ORCID Profile
0000-0003-4046-8276
Current Organisations
Monash University
,
National Health and Medical Research Council
,
Victoria University
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Research Topics
In Research Link Australia (RLA), "Research Topics" refer to ANZSRC FOR and SEO codes. These topics are either sourced from ANZSRC FOR and SEO codes listed in researchers' related grants or generated by a large language model (LLM) based on their publications.
Top 5 Research Topics
ANZSRC Field of Research (FoR)
Exercise Physiology | Epigenetics (incl. Genome Methylation and Epigenomics) | Genetics | Preventive Medicine | Genomics | Human Movement and Sports Science | Population, Ecological and Evolutionary Genetics | Cell Metabolism
ANZSRC Socio-Economic Objective (SEO)
Expanding Knowledge in the Medical and Health Sciences | Expanding Knowledge in the Biological Sciences | Public Health (excl. Specific Population Health) not elsewhere classified |
Related Links
Publications
Methylome and proteome integration in human skeletal muscle uncover group and individual responses to high‐intensity interval training
Publisher: Wiley
Date: 12-09-2023
Meta-analysis of genome-wide DNA methylation and integrative omics of age in human skeletal muscle
Publisher: Wiley
Date: 30-06-2021
DOI: 10.1002/JCSM.12741
Abstract: Knowledge of age‐related DNA methylation changes in skeletal muscle is limited, yet this tissue is severely affected by ageing in humans. We conducted a large‐scale epigenome‐wide association study meta‐analysis of age in human skeletal muscle from 10 studies (total n = 908 muscle methylomes from men and women aged 18–89 years old). We explored the genomic context of age‐related DNA methylation changes in chromatin states, CpG islands, and transcription factor binding sites and performed gene set enrichment analysis. We then integrated the DNA methylation data with known transcriptomic and proteomic age‐related changes in skeletal muscle. Finally, we updated our recently developed muscle epigenetic clock ( ackages/release/bioc/html/MEAT.html ). We identified 6710 differentially methylated regions at a stringent false discovery rate .005, spanning 6367 unique genes, many of which related to skeletal muscle structure and development. We found a strong increase in DNA methylation at Polycomb target genes and bivalent chromatin domains and a concomitant decrease in DNA methylation at enhancers. Most differentially methylated genes were not altered at the mRNA or protein level, but they were nonetheless strongly enriched for genes showing age‐related differential mRNA and protein expression. After adding a substantial number of s les from five datasets (+371), the updated version of the muscle clock (MEAT 2.0, total n = 1053 s les) performed similarly to the original version of the muscle clock (median of 4.4 vs. 4.6 years in age prediction error), suggesting that the original version of the muscle clock was very accurate. We provide here the most comprehensive picture of DNA methylation ageing in human skeletal muscle and reveal widespread alterations of genes involved in skeletal muscle structure, development, and differentiation. We have made our results available as an open‐access, user‐friendly, web‐based tool called MetaMeth ( sarah‐voisin.shinyapps.io/MetaMeth/ ).
Genetic variants within the COL5A1 gene are associated with ligament injuries in physically active populations from Australia, South Africa, and Japan
Publisher: Informa UK Limited
Date: 30-12-2021
DOI: 10.1080/17461391.2021.2011426
Abstract: Previous small-scale studies have shown an association between the
More than a ‘speed gene’: ACTN3 R577X genotype, trainability, muscle damage, and the risk for injuries
Publisher: Springer Science and Business Media LLC
Date: 16-10-2018
DOI: 10.1007/S00421-018-4010-0
Abstract: A common null polymorphism (rs1815739 R577X) in the gene that codes for α-actinin-3 (ACTN3) has been related to different aspects of exercise performance. In iduals who are homozygous for the X allele are unable to express the α-actinin-3 protein in the muscle as opposed to those with the RX or RR genotype. α-actinin-3 deficiency in the muscle does not result in any disease. However, the different ACTN3 genotypes can modify the functioning of skeletal muscle during exercise through structural, metabolic or signaling changes, as shown in both humans and in the mouse model. Specifically, the ACTN3 RR genotype might favor the ability to generate powerful and forceful muscle contractions. Leading to an overall advantage of the RR genotype for enhanced performance in some speed and power-oriented sports. In addition, RR genotype might also favor the ability to withstand exercise-induced muscle damage, while the beneficial influence of the XX genotype on aerobic exercise performance needs to be validated in human studies. More information is required to unveil the association of ACTN3 genotype with trainability and injury risk during acute or chronic exercise.
The champions' mitochondria: is it genetically determined? A review on mitochondrial DNA and elite athletic performance
Publisher: American Physiological Society
Date: 07-2011
DOI: 10.1152/PHYSIOLGENOMICS.00029.2011
Abstract: Aerobic ATP generation by the mitochondrial respiratory oxidative phosphorylation system (OXPHOS) is a vital metabolic process for endurance exercise. Notably, mitochondrial DNA (mtDNA) codifies 13 of the 83 polypeptides implied in the respiratory chain. As such, there is a strong rationale for identifying an association between mtDNA variants and “aerobic” (endurance) exercise phenotypes. The aim of this review is to summarize current knowledge on the association between mtDNA, nuclear genes involved in mitochondriogenesis, and elite endurance athletic status. Several studies in nonathletic people have demonstrated an association between certain mtDNA lineages and aerobic performance, characterized by maximal oxygen uptake (V̇o 2max ). Whether mtDNA haplogroups are also associated with the status of being an elite endurance athlete is more controversial, with differences between studies arising from the different ethnic backgrounds of the athletic cohorts (Caucasian of mixed geographic origin, Asiatic, or East African).
GNAS A-1121G Variant is Associated with Improved Diastolic Dysfunction in Response to Exercise Training in Heart Failure Patients
Publisher: Georg Thieme Verlag KG
Date: 12-10-2012
Abstract: β1-adrenergic receptors (ADRB1) and Gαs proteins (GNAS) play important roles in the regulation of cardiac function. The present study sought to investigate whether ADRB1 Arg389Gly (rs1801253), GNAS -1211 G/A (rs6123837) and GNAS 2291 C/T (rs6026584) variants are associated with left ventricular function and exercise tolerance in heart failure patients. 61 heart failure patients completed a 6-month exercise-training programme. Left ventricular ejection fraction (LVEF), mitral inflow velocities (deceleration time, and E/A ratio) and exercise tolerance (METs) were assessed at baseline and following exercise training. There were no associations between the studied variants and LVEF or E/A ratio measured at baseline and after exercise training. Deceleration time of early mitral flow was higher at baseline in GNAS -1211G allele carriers compared with -1211A allele homozygotes (P<0.05). Exercise training attenuated deceleration time in -1211G allele carriers (P<0.05) but not in -1211A allele homozygotes. Moreover, ADRB1 389Gly homozygotes had a greater training-induced increase in exercise tolerance than 389Arg homozygotes (P=0.04). This study shows that the functional GNAS -1121 G/A polymorphism is associated with diastolic function at baseline and in response to exercise training in heart failure patients. Furthermore, our data suggest that ADRB1 Arg389Gly polymorphism may influence exercise tolerance.
TheACEdeletion allele is associated with Israeli elite endurance athletes
Publisher: Wiley
Date: 29-08-2007
DOI: 10.1113/EXPPHYSIOL.2007.038711
Abstract: An Alu insertion (I)/deletion (D) polymorphism in the angiotensin I converting enzyme (ACE) gene has been associated with ACE activity. Opposing effects on elite athletic performance have been proposed for the I and D alleles while the D allele favours improved endurance ability, the I allele promotes more power-orientated events. We tested this hypothesis by determining the frequency of ACE ID alleles amongst 121 Israeli top-level athletes classified by their sporting discipline (marathon runners or sprinters). Genotyping for ACE ID was performed using polymerase chain reaction on DNA from leucocytes. The ACE genotype and allele frequencies were compared with those of 247 healthy in iduals. Allele and genotype frequencies differed significantly between the groups. The frequency of the D allele was 0.77 in the marathon runners, 0.66 in the control subjects (P = 0.01) and 0.57 in the sprinters (P = 0.002). The ACE DD genotype was more prevalent among the endurance athletes (0.62) than among the control subjects (0.43, P = 0.004) and the power athletes (0.34, P = 0.004). In the group of elite athletes, the odds ratio of ACE DD genotype being an endurance athlete was 3.26 (95% confidence interval 1.49-7.11), and of ACE II genotype was 0.41 (95% confidence interval 0.14-1.19). We conclude that in Israeli elite marathon runners the frequency of the ACE D allele and ACE DD genotype seems to be higher than in sprinters, suggesting a positive association between the D allele and the likelihood of being an elite endurance athlete in some ethnic groups.
ACVR1B rs2854464 Is Associated with Sprint/Power Athletic Status in a Large Cohort of Europeans but Not Brazilians
Publisher: Public Library of Science (PLoS)
Date: 02-06-2016
EPAS1 gene variants are associated with sprint/power athletic performance in two cohorts of European athletes
Publisher: Springer Science and Business Media LLC
Date: 18-05-2014
Sex differences in muscle protein expression and DNA methylation in response to exercise training
Publisher: Springer Science and Business Media LLC
Date: 05-09-2023
Genetic Aspects of Sprint, Strength and Power Performance
Publisher: Elsevier
Date: 2013
The guanine nucleotide binding protein β polypeptide 3 gene C825T polymorphism is associated with elite endurance athletes
Publisher: Wiley
Date: 13-02-2009
DOI: 10.1113/EXPPHYSIOL.2008.045138
Abstract: A functional C825T polymorphism in the human guanine nucleotide binding protein beta polypeptide 3 (GNB3) gene has been associated with enhanced G protein activation. Since reports regarding the interaction between physical activity and the GNB3 C825T polymorphism are limited and inconsistent, the aim of this study was to determine the frequency of C825T alleles among 155 elite Israeli athletes (endurance athletes and sprinters) and 234 healthy control subjects. Genotyping for GNB3 C825T was performed using polymerase chain reaction on DNA from leucocytes. Results showed that there was a significant difference in GNB3 C825T polymorphism genotype frequencies between endurance athletes and sprinters (P = 0.045) as well as between endurance athletes and control subjects (P = 0.046). We also observed a significantly higher proportion of the GNB3 TT genotype in the group of endurance athletes (19%) compared with the sprinters (5%, P = 0.014) and the control subjects (8.5%, P = 0.026). In the group of athletes, the odds ratio of GNB3 TT genotype being an endurance athlete was 4.49 (95% confidence interval 1.4-14.3) and of GNB3 CC genotype was 0.91 (95% confidence interval 0.47-1.77). These results were even more pronounced when we compared between the subgroups of 20 top-level endurance athletes and 24 top-level sprinters. We conclude that in Israeli athletes the GNB3 TT genotype is higher in elite endurance athletes than it is in sprinters, and within the endurance group it is higher in top-level athletes, suggesting a positive association between the TT genotype and the likelihood of being an elite endurance athlete.
A Multi-Center Comparison of O2peak Trainability Between Interval Training and Moderate Intensity Continuous Training
Publisher: Frontiers Media SA
Date: 05-02-2019
Individual physiological and mitochondrial responses during 12 weeks of intensified exercise
Publisher: Wiley
Date: 29-07-2021
DOI: 10.14814/PHY2.14962
Preface: genomics and biology of exercise is undergoing a paradigm shift
Publisher: Springer Science and Business Media LLC
Date: 11-2017
Aerobic capacity and telomere length in human skeletal muscle and leukocytes across the lifespan
Publisher: Impact Journals, LLC
Date: 03-01-2020
PPARAintron 1 A/C polymorphism and elite athlete status
Publisher: Informa UK Limited
Date: 05-2011
The Impact of Gender-Affirming Hormone Therapy on Physical Performance
Publisher: The Endocrine Society
Date: 13-07-2023
Abstract: The inclusion of transgender people in elite sport has been a topic of debate. This narrative review examines the impact of gender-affirming hormone therapy (GAHT) on physical performance, muscle strength, and markers of endurance. MEDLINE and Embase were searched using terms to define the population (transgender), intervention (GAHT), and physical performance outcomes. Existing literature comprises cross-sectional or small uncontrolled longitudinal studies of short duration. In nonathletic trans men starting testosterone therapy, within 1 year, muscle mass and strength increased and, by 3 years, physical performance (push-ups, sit-ups, run time) improved to the level of cisgender men. In nonathletic trans women, feminizing hormone therapy increased fat mass by approximately 30% and decreased muscle mass by approximately 5% after 12 months, and steadily declined beyond 3 years. While absolute lean mass remains higher in trans women, relative percentage lean mass and fat mass (and muscle strength corrected for lean mass), hemoglobin, and VO2 peak corrected for weight was no different to cisgender women. After 2 years of GAHT, no advantage was observed for physical performance measured by running time or in trans women. By 4 years, there was no advantage in sit-ups. While push-up performance declined in trans women, a statistical advantage remained relative to cisgender women. Limited evidence suggests that physical performance of nonathletic trans people who have undergone GAHT for at least 2 years approaches that of cisgender controls. Further controlled longitudinal research is needed in trans athletes and nonathletes.
Physiological variables and mitochondrial-related genotypes of an athlete who excels in both short and long-distance running
Publisher: Elsevier BV
Date: 09-2011
DOI: 10.1016/J.MITO.2011.05.009
Abstract: We report the athletic, physiological and mitochondrial-related genomic data of an Israeli endurance runner. He is holding the Israeli record in 10,000, 5000, 1500 and 800 m run, along with being one of the best Israeli 400 m runners. We tested the ACTN3 R577X, and six polymorphisms in the PPARGC1A-NRF-TFAM pathway genes. The case athlete was heterozygous for the ACTN3 R577X variation and had five out of six 'endurance-oriented' genotypes, scoring significantly high in endurance 'optimal' genotype profile. In conclusion, we suggest that the case athlete is favoured by polygenic profile that is more suitable for mitochondrial biogenesis, regardless of his good phenotypic accomplishments in short-term running events.
Integrative transcriptomic and proteomic analysis show circulating osteoprogenitors to have a mixed immune and mesenchymal progenitor function in humans
Publisher: Research Square Platform LLC
Date: 17-10-2022
DOI: 10.21203/RS.3.RS-2160180/V1
Abstract: Circulating osteoprogenitors (COP) is a population of cells in the peripheral circulation that possess functional and phenotypical characteristics of multipotent stromal cells (MSCs). While there is functional overlap, it is not known how COP cells are related to bone marrow (BM)-derived MSCs (BM-MSCs) and other better characterized stromal progenitor populations such as adipose-derived stromal cells (ASCs). This study compares COP cells to BM-MSCs and ASCs through detailed transcriptomic and proteomic analyses. COP cells have a distinct gene and protein expression pattern to BM-MSCs and ASCs, with a significantly stronger immune footprint, likely owing to their hematopoietic lineage. However, they also have a similar pattern of expression BM-MSCs and ASCs, in genes and proteins in progenitor cell differentiation and proliferation pathways. This study shows COP cells to be a unique but functionally similar population to BM-MSCs and ASCs, sharing their proliferation and differentiation capacity, but with a strong immune phenotype, with potential for translational regenerative medicine strategies.
Circulating osteoprogenitors have a mixed immune and mesenchymal progenitor function in humans
Publisher: Research Square Platform LLC
Date: 18-10-2022
DOI: 10.21203/RS.3.RS-2160180/V2
Abstract: Circulating osteoprogenitors (COP) are a population of cells in the peripheral circulation that possess functional and phenotypical characteristics of multipotent stromal cells (MSCs). These cells can differentiate into adipocyte, chondrocyte, myocyte, and osteoblast lineages. Considering that COP cells are isolated from peripheral blood, this population has a strong potential to become an abundant, accessible, and replenishable source of MSCs with multiple potential clinical applications for the repair and regeneration of acute and chronically damaged tissues. However, in order to fully test and develop their use in clinical settings, a comprehensive functional characterization of COP cells is still required. This study fully characterized COP cells by comparing them to bone marrow-derived MSCs (BM-MSCs) and adipose-derived MSCs (ASCs) through detailed transcriptomic and proteomic analyses. COP cells have a distinct gene and protein expression pattern to BM-MSCs and ASCs, with a significantly stronger immune footprint, likely owing to their hematopoietic lineage. In addition, regarding progenitor cell differentiation and proliferation pathways, COP cells have a similar pattern of expression to BM-MSCs and ASCs. In summary, this study shows COP cells to be a unique but functionally similar population to BM-MSCs and ASCs, sharing their proliferation and differentiation capacity, thus presenting an accessible source of MSCs with strong potential for translational regenerative medicine strategies.
No Evidence of a Common DNA Variant Profile Specific to World Class Endurance Athletes
Publisher: Public Library of Science (PLoS)
Date: 29-01-2016
DoPPARGC1AandPPARαpolymorphisms influence sprint or endurance phenotypes?
Publisher: Wiley
Date: 02-2010
DOI: 10.1111/J.1600-0838.2009.00930.X
Abstract: Functional Gly482Ser (rs8192678) and G/C (rs4253778) polymorphisms in the Peroxisome proliferator-activated receptor gamma coactivator1 (PPARGC1A) and Peroxisome proliferator-activated receptor alpha (PPARalpha) genes, respectively, have been associated with mRNA and protein activity. The aim of this study was to determine their frequency distribution among 155 Israeli athletes (endurance athletes and sprinters) and 240 healthy controls. Results showed that there was a significant difference in PPARGC1A Ser482Gly polymorphism genotype frequencies between endurance athletes and sprinters (P=0.005) as well as between endurance athletes and controls (P=0.0003). However, the sprinters' genotype and allele frequencies were similar to that of the control group. A significantly lower proportion of PPARGC1A Ser482 allele (0.25) was noted for the endurance athletes compared with controls (0.43, P=0.0001). Endurance athletes showed a trend of a higher yet a not significant proportion of the PPARalpha GG genotype compared with sprinters (P=0.051). As we compared between the subgroups of top-level endurance athletes and top-level sprinters, as well as between those of top-level and national-level endurance athletes, we reached more prominent results. In conclusion, our data indicate that a lower frequency of the Ser482 allele and possibly a higher frequency of the GG genotype are associated with increased endurance performance ability.
Is the interaction between HIF1A P582S and ACTN3 R577X determinant for power/sprint performance?
Publisher: Elsevier BV
Date: 06-2010
DOI: 10.1016/J.METABOL.2009.10.003
Abstract: Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that regulates gene expression in response to hypoxia and has been associated with athletic performance. The aims of this study were (1) to determine the frequency distribution of HIF1A Pro582Ser (rs11549465) polymorphism among 155 Israeli athletes (sprinters and endurance athletes) and 240 healthy controls and (2) to analyze the influence of the interaction between HIF1A Pro582Ser and ACTN3 R577X (rs1815739) genotypes on sprint performance. There were no differences across the HIF1A genotype and allele frequencies among endurance athletes, sprinters, and controls. Similarly, no differences were found between the subgroups of top-level and national-level endurance athletes, or between top-level and national-level sprinters. Conversely, interaction effects were found between HIF1A Pro582Ser and ACTN3 R577X polymorphisms and sprinters. The proportion of HIF1A Pro/Pro + ACTN3 R/R genotypes was significantly higher in sprinters than in endurance athletes and healthy controls (P = .002). In addition, the odds ratio for HIF1A Pro/Pro + ACTN3 R/R genotype carriers being a sprinter was 2.25 (95% confidence interval, 1.24-4.1) and that for HIF1A Pro/Pro + ACTN3 R/R genotype carriers being an endurance athlete was 0.5 (95% confidence interval, 0.2-1.24). We conclude that HIF1A Pro582Ser polymorphism by itself is not critical in determining sprint performance. However, sprinter performance is determined by the interaction between the wild-type HIF1A Pro/Pro genotype and ACTN3 RR genotype.
PGC-related gene variants and elite endurance athletic status in a Chinese cohort: A functional study
Publisher: Wiley
Date: 20-02-2014
DOI: 10.1111/SMS.12188
Abstract: This study aims to examine the association between proliferator-activated receptor γ (PGC)-gene family-related single nucleotide polymorphisms (SNPs) and elite endurance runners' status in a Chinese cohort, and to gain insights into the functionality of a subset of SNPs. Genotype distributions of 133 SNPs in PPARGC1A, PPARGC1B, PPRC1, TFAM, TFB1M, TFB2M, NRF1, GABPA, GABPB1, ERRα, and SIRT1 genes were compared between 235 elite Chinese (Han) endurance runners (127 women) and 504 healthy non-athletic controls (237 women). Luciferase gene reporter activity was determined in 20 SNPs. After adjusting for multiple comparisons (in which threshold P-value was set at 0.00041), no significant differences were found in allele/genotype frequencies between athletes and controls (when both sexes were analyzed either together or separately). The lowest P-value was found in PPARGC1A rs4697425 (P = 0.001 for the comparison of allele frequencies between elite female endurance runners and their gender-matched controls). However, no association (all P > 0.05) was observed for this SNP in a replication cohort from Poland (194 endurance athletes and 190 controls). Using functional genomics tool, the following SNPs were found to have functional significance: PPARGC1A rs6821591, rs12650562, rs12374310, rs4697425, rs13113110, and rs4452416 PPARGC1B rs251466 and rs17110586 and PPRC1 rs17114388 (all P < 0.001). This study found no significant association between PGC-related SNPs and elite endurance athlete status in the Chinese population, despite some SNPs showing potential functional significance and the strong biological rationale to hypothesize that this gene pathway is a candidate to influence endurance exercise capacity.
The C Allele in NOS3 -786 T/C Polymorphism is Associated with Elite Soccer Player's Status
Publisher: Georg Thieme Verlag KG
Date: 12-04-2012
Abstract: The NOS3-786 T/C polymorphism (rs2070744) is a candidate to explain in idual variations in sports related phenotypes. We determined the genotype and allele frequency of NOS3-786 T/C in a group of 60 male professional elite soccer players. Their results were compared with those of 100 world-class endurance athletes, 53 elite power athletes, and 100 sedentary, healthy men (controls) of the same Caucasian (Spanish) origin. There were significant differences in genotype frequencies between soccer players, controls, endurance and power elite athletes (all P ≤ 0.02). These results were confirmed when we analysed allelic frequencies (all P<0.01). The likelihood of having the C allele was higher in soccer players compared with (i) controls [odds ratio (OR), 2.165, 95% confidence interval (CI): 1.362-3.441], (ii) endurance athletes (OR: 1.879, 95%CI: 1.184-2.984), and (iii) power athletes (OR: 4.032, 95%CI: 2.307-7.047). In conclusion, the -786C allele is associated with the status of being an elite soccer player, compared with non-athletic controls and also with elite endurance and power athletes. More research is needed in other groups of elite soccer players in order to replicate the results of the present study.
ACE I/D gene variant predicts ACE enzyme content in blood but not the ACE, UCP2, and UCP3 protein content in human skeletal muscle in the Gene SMART study
Publisher: American Physiological Society
Date: 09-2018
DOI: 10.1152/JAPPLPHYSIOL.00344.2018
Abstract: Angiotensin-converting enzyme (ACE) is expressed in human skeletal muscle. The ACE I/D polymorphism has been associated with athletic performance in some studies. Studies have suggested that the ACE I/D gene variant is associated with ACE enzyme content in serum, and there is an interaction between ACE and uncoupling proteins 2 and 3 (UCP2 and UCP3). However, no studies have explored the effect of ACE I/D on ACE, UCP2, and UCP3 protein content in human skeletal muscle. Utilizing the Gene SMART cohort ( n = 81), we investigated whether the ACE I/D gene variant is associated with ACE enzyme content in blood and ACE, UCP2, and UCP3 protein content in skeletal muscle at baseline and following a session of high-intensity interval exercise (HIIE). Using a stringent and robust statistical analyses, we found that the ACE I/D gene variant was associated with ACE enzyme content in blood ( P 0.005) at baseline but not the ACE, UCP2, and UCP3 protein content in muscle at baseline. A single session of HIIE tended (0.005 P 0.05) to increase blood ACE content immediately postexercise, whereas muscle ACE protein content was lower 3 h after a single session of HIIE ( P 0.005). Muscle UCP3 protein content decreased immediately after a single session of HIIE ( P 0.005) and remained low 3 h postexercise. However, those changes in the muscle were not genotype dependent. In conclusion, The ACE I/D gene variant predicts ACE enzyme content in blood but not the ACE, UCP2, and UCP3 protein content of human skeletal muscle. NEW & NOTEWORTHY This paper describes the association between ACE I/D gene variant and ACE protein content in blood and ACE, UCP2, and UCP3 protein content in skeletal muscle at baseline and after exercise in a large cohort of healthy males. Our data suggest that ACE I/D is a strong predictor of blood ACE content but not muscle ACE content.
GNB3C825T Polymorphism and Elite Athletic Status: A Replication Study with Two Ethnic Groups
Publisher: Georg Thieme Verlag KG
Date: 25-11-2010
Abstract: We aimed to replicate the original findings by Eynon et al. showing an association between the T allele of the GNB3 C825T polymorphism and elite endurance athletic status, in larger cohorts and in other ethnicities. We compared allelic and genotypic frequencies of the GNB3 C825T polymorphism among non-athletic controls (N=340), elite endurance athletes (N=174), and power athletes (N=134). The population s le included participants from 2 different ethnic/geographic backgrounds (Israel and Spain). We observed no significant differences in genotypic and allelic frequencies between countries or groups (all P>0.1). The odds ratio (OR) of being an endurance athlete if the subject had a T allele was 0.841 (95%CI: 0.638-1.110) compared to the control group and 1.047 (95% CI: 0.751-1.461) compared to the power group. Our findings support the need to corroborate genotype:phenotype associations in the field of sports genetics with the largest possible population s les, including populations of different ethnic backgrounds.
NRF2intron 3 A/G polymorphism is associated with endurance athletes’ status
Publisher: American Physiological Society
Date: 07-2009
DOI: 10.1152/JAPPLPHYSIOL.00310.2009
Abstract: The aim of this study was to determine the frequency distribution of nuclear respiratory factor 2 ( NRF2) intron 3 A/G polymorphism (rs7181866) among 155 Israeli athletes (endurance athletes and sprinters) and 240 healthy controls. Results showed that there was a significantly higher proportion of the AG genotype, rather than the AA genotype, in the group of endurance athletes compared with the sprinters ( P = 0.014) and controls ( P = 0.0008). However, the sprinters’ genotype and allele frequencies were similar to those of the control group ( P = 0.62 for genotype distribution percentage). These results were even more pronounced when we compared between the subgroups of 20 elite endurance athletes (those who had represented Israel in a world track-and-field ch ionship or in the Olympic Games) and 54 national-level endurance athletes. In the group of elite endurance athletes the G allele was more frequent than in the national-level endurance athletes ( P = 0.047). We conclude that 1) in Israeli athletes the NRF2 AG genotype is more frequent in elite endurance athletes than in sprinters, and 2) within the endurance group the NRF2 AG genotype and the G allele are more frequent in elite athletes, suggesting a positive association between the AG genotype, and possibly the G allele, and the likelihood of being an elite endurance athlete.
Genes to predict VO2max trainability: a systematic review.
Publisher: Springer Science and Business Media LLC
Date: 11-2017
The Future of Genomic Research in Athletic Performance and Adaptation to Training
Publisher: S. Karger AG
Date: 2016
DOI: 10.1159/000445241
Abstract: Despite numerous attempts to discover genetic variants associated with elite athletic performance, an in idual's trainability and injury predisposition, there has been limited progress to date. Past reliance on candidate gene studies focusing predominantly on genotyping a limited number of genetic variants in small, often heterogeneous cohorts has not generated results of practical significance. Hypothesis-free genome-wide approaches will in the future provide more comprehensive coverage and in-depth understanding of the biology underlying sports-related traits and related genetic mechanisms. Large, collaborative projects with sound experimental designs (e.g. clearly defined phenotypes, considerations and controls for sources of variability, and necessary replications) are required to produce meaningful results, especially when a hypothesis-free approach is used. It remains to be determined whether the novel approaches under current implementation will result in findings with real practical significance. This review will briefly summarize current and future directions in exercise genetics and genomics.
Genes for Elite Power and Sprint Performance: ACTN3 Leads the Way
Publisher: Springer Science and Business Media LLC
Date: 17-05-2013
DOI: 10.1007/S40279-013-0059-4
Abstract: The ability of skeletal muscles to produce force at a high velocity, which is crucial for success in power and sprint performance, is strongly influenced by genetics and without the appropriate genetic make-up, an in idual reduces his/her chances of becoming an exceptional power or sprinter athlete. Several genetic variants (i.e. polymorphisms) have been associated with elite power and sprint performance in the last few years and the current paradigm is that elite performance is a polygenic trait, with minor contributions of each variant to the unique athletic phenotype. The purpose of this review is to summarize the specific knowledge in the field of genetics and elite power performance, and to provide some future directions for research in this field. Of the polymorphisms associated with elite power and sprint performance, the α-actinin-3 R577X polymorphism provides the most consistent results. ACTN3 is the only gene that shows a genotype and performance association across multiple cohorts of elite power athletes, and this association is strongly supported by mechanistic data from an Actn3 knockout mouse model. The angiotensin-1 converting enzyme insertion/deletion polymorphism (ACE I/D, registered single nucleotide polymorphism [rs]4646994), angiotensinogen (AGT Met235Thr rs699), skeletal adenosine monophosphate deaminase (AMPD1) Gln(Q)12Ter(X) [also termed C34T, rs17602729], interleukin-6 (IL-6 -174 G/C, rs1800795), endothelial nitric oxide synthase 3 (NOS3 -786 T/C, rs2070744 and Glu298Asp, rs1799983), peroxisome proliferator-activated receptor-α (PPARA Intron 7 G/C, rs4253778), and mitochondrial uncoupling protein 2 (UCP2 Ala55Val, rs660339) polymorphisms have also been associated with elite power performance, but the findings are less consistent. In general, research into the genetics of athletic performance is limited by a small s le size in in idual studies and the heterogeneity of study s les, often including athletes from multiple-difference sporting disciplines. In the future, large, homogeneous, strictly defined elite power athlete cohorts need to be established though multinational collaboration, so that meaningful genome-wide association studies can be performed. Such an approach would provide unbiased identification of potential genes that influence elite athletic performance.
Meta-analysis of genome-wide DNA methylation and integrative OMICs in human skeletal muscle
Publisher: Cold Spring Harbor Laboratory
Date: 28-09-2020
DOI: 10.1101/2020.09.28.315838
Abstract: Knowledge of age-related DNA methylation changes in skeletal muscle is limited, yet this tissue is severely affected by aging in humans. Using a large-scale epigenome-wide association study (EWAS) meta-analysis of age in human skeletal muscle from 10 studies (total n = 908 human muscle methylomes), we identified 9,986 differentially methylated regions at a stringent false discovery rate 0.005, spanning 8,748 unique genes, many of which related to skeletal muscle structure and development. We then integrated the DNA methylation results with known transcriptomic and proteomic age-related changes in skeletal muscle, and found that even though most differentially methylated genes are not altered at the mRNA or protein level, they are nonetheless strongly enriched for genes showing age-related differential expression. We provide here the most comprehensive picture of DNA methylation aging in human skeletal muscle, and have made our results available as an open-access, user-friendly, web-based tool called MetaMeth ( sarah-voisin.shinyapps.io/MetaMeth/ ).
Epigenetic changes in healthy human skeletal muscle following exercise– a systematic review
Publisher: Informa UK Limited
Date: 13-05-2019
The influence of α-actinin-3 deficiency on bone remodelling markers in young men
Publisher: Elsevier BV
Date: 05-2017
DOI: 10.1016/J.BONE.2017.02.010
Abstract: There is a large in idual variation in the bone remodelling markers (BRMs) osteocalcin (OC), procollagen 1 N-terminal propeptide (P1NP) and β-isomerized C-terminal telopeptide (β-CTx), as well as undercarboxylated osteocalcin (ucOC), at rest and in response to exercise. α-actinin-3 (ACTN3), a sarcomeric protein, is expressed in skeletal muscle and osteoblasts and may influence BRM levels and the cross-talk between muscle and bone. We tested the levels of serum BRMs in α-actinin-3 deficient humans (ACTN3 XX) at baseline, and following a single bout of exercise. Forty-three healthy Caucasian in iduals were ided into three groups (ACTN3 XX, n=13 ACTN3 RX, n=16 ACTN3 RR, n=14). Participants completed a single session of High Intensity Interval Exercise (HIIE) on a cycle ergometer (8×2-min intervals at 85% of maximal power). Blood s les were taken before, immediately after, and three hours post exercise to identify the peak changes in serum BRMs. There was a stepwise increase in resting serum BRMs across the ACTN3 genotypes (XX>RX>RR) with significantly higher levels of tOC ~26%, P1NP ~34%, and β-CTX (~33%) in those with ACTN3 XX compared to ACTN3 RR. Following exercise BRMs and ucOC were higher in all three ACTN3 genotypes, with no significant differences between groups. Serum levels of tOC, P1NP and β-CTX are higher in men with ACTN3 XX genotype (α-actinin-3 deficiency) compared to RR and RX. It appears that the response of BRMs and ucOC to exercise is not explained by the ACTN3 genotype.
Genes and elite athletes: a roadmap for future research
Publisher: Wiley
Date: 29-06-2011
Is there an interaction between BDKRB2−9/+9 and GNB3 C825T polymorphisms and elite athletic performance?
Publisher: Wiley
Date: 07-01-2011
DOI: 10.1111/J.1600-0838.2010.01261.X
Abstract: The -9 deletion allele in the BDKRB2 -9/+9 polymorphism was associated previously with improved endurance performance. We compared the frequency distribution of the BDKRB2 -9/+9 (rs5810761) polymorphism between athletes (n=155) of sports with different demands (endurance runners n=74 vs sprinters n=81) as well as between athletes of different competitive levels (elite level n=46 vs national level n=109). These results were compared with those of 240 non-athletic healthy in iduals. We also tested the influence of the interaction between the BDKRB2 -9/+9 and the GNB3 C825T (rs5443) genotypes in relation to endurance performance. Genotype distribution and allele frequencies were found to be similar in the endurance athlete, sprinter, and control groups (P=0.83 for genotype distribution and P=0.9 for allele frequencies). Similarly, no statistical differences were found between the subgroups of elite-level endurance athletes and national-level endurance athletes, or between elite-level and national-level sprinters (P>0.09 for all comparisons). There was no interaction between BDKRB2 -9/+9 and GNB3 C825T polymorphisms in relation to endurance performance (P=0.16 for interaction effect). In conclusion, the BDKRB2 +9/-9 polymorphism is not associated with endurance performance, at least among Israeli athletes, and the GNB3TT+BDKRB2 -9/-9 "optimal genotype" is not associated with endurance performance.
Genomics of Elite Sporting Performance
Publisher: Elsevier
Date: 2013
Investigating the influence of mtDNA and nuclear encoded mitochondrial variants on high intensity interval training outcomes
Publisher: Springer Science and Business Media LLC
Date: 06-07-2020
DOI: 10.1038/S41598-020-67870-1
Abstract: Mitochondria supply intracellular energy requirements during exercise. Specific mitochondrial haplogroups and mitochondrial genetic variants have been associated with athletic performance, and exercise responses. However, these associations were discovered using underpowered, candidate gene approaches, and consequently have not been replicated. Here, we used whole-mitochondrial genome sequencing, in conjunction with high-throughput genotyping arrays, to discover novel genetic variants associated with exercise responses in the Gene SMART (Skeletal Muscle Adaptive Response to Training) cohort (n = 62 completed). We performed a Principal Component Analysis of cohort aerobic fitness measures to build composite traits and test for variants associated with exercise outcomes. None of the mitochondrial genetic variants but eight nuclear encoded variants in seven separate genes were found to be associated with exercise responses (FDR 0.05) ( rs11061368 : DIABLO , rs113400963 : FAM185A , rs6062129 and rs6121949 : MTG2 , rs7231304 : AFG3L2 , rs2041840 : NDUFAF7 , rs7085433 : TIMM23 , rs1063271 : SPTLC2 ) . Additionally, we outline potential mechanisms by which these variants may be contributing to exercise phenotypes. Our data suggest novel nuclear-encoded SNPs and mitochondrial pathways associated with exercise response phenotypes. Future studies should focus on validating these variants across different cohorts and ethnicities.
Corrigendum
Publisher: American Physiological Society
Date: 09-2010
ACTN3 R577X Polymorphism Is Associated With the Incidence and Severity of Injuries in Professional Football Players
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2019
The association between bone mineral density gene variants and osteocalcin at baseline, and in response to exercise: The Gene SMART study
Publisher: Elsevier BV
Date: 06-2019
DOI: 10.1016/J.BONE.2019.03.015
Abstract: Osteocalcin (OC) is used as a surrogate marker for bone turnover in clinical settings. As bone mineral density (BMD) is largely heritable, we tested the hypothesis that a) bone-associated genetic variants previously identified in Genome-Wide Association Studies (GWAS) and combined into a genetic risk score (GRS) are associated with a) circulating levels of OC and b) the changes in OC following acute exercise. Total OC (tOC), undercarboxylated OC (ucOC), and carboxylated OC (cOC) were measured in serum of 73 healthy Caucasian males at baseline and after a single bout of high-intensity interval exercise. In addition, genotyping was conducted targeting GWAS variants previously reported to be associated with BMD and then combined into a GRS. Potential associations between the GRS and tOC, ucOC and cOC were tested with linear regressions adjusted for age. At baseline none of the in idual SNPs associated with tOC, ucOC and cOC. However, when combined, a higher GRS was associated with higher tOC (β = 0.193 ng/mL p = 0.037 95% CI = 0.012, 0.361) and cOC (β = 0.188 ng/mL p = 0.04 95% CI = 0.004, 0.433). Following exercise, GRS was associated with ucOC levels, (β = 3.864 ng/mL p-value = 0.008 95% CI = 1.063, 6.664) but not with tOC or cOC. Screening for genetic variations may assist in identifying people at risk for abnormal circulating levels of OC at baseline/rest. Genetic variations in BMD predicted the ucOC response to acute exercise indicating that physiological functional response to exercise may be influenced by bone-related gene variants.
The rs12594956 polymorphism in the NRF-2 gene is associated with top-level Spanish athlete's performance status
Publisher: Elsevier BV
Date: 03-2013
DOI: 10.1016/J.JSAMS.2012.05.004
Abstract: To determine the association between the nuclear respiratory factor 2 (NRF-2) polymorphisms and elite athletic performance. We compared the genotype and allele frequencies of the NRF-2 A/C (rs12594956), NRF-2 A/G (rs7181866), and NRF-2 C/T (rs8031031) polymorphisms between world-class endurance athletes (n=89), elite power-oriented athletes (n=38), and non-athletic controls (n=110) of the same Caucasian (Spanish) origin. Genomic DNA was extracted from peripheral EDTA-treated, anti-coagulated blood using a standard protocol. Genotyping was performed using polymerase chain reaction (PCR). The frequency of the AA genotype of the NRF-2 A/C (rs12594956) polymorphism was significantly higher in endurance athletes compared with power athletes (P<0.01) and controls (P<0.01) (48% vs. 13% and 21%, respectively). The likelihood of having the AA (rs12594956) genotype was higher in elite endurance athletes compared with controls [odds ratio (OR): 3.536, 95% confidence interval (CI): 1.903-6.571] and elite power athletes (OR: 6.170, 95%CI: 2.206-17.253). Our results suggest that the NRF-2 A/C polymorphism might belong to a growing group of polymorphisms associated with endurance performance at the elite level. However, it is important to replicate these findings in other groups of elite athletes using larger s le sizes.
Genetic testing for exercise prescription and injury prevention: AIS-Athlome consortium-FIMS joint statement
Publisher: Springer Science and Business Media LLC
Date: 11-2017
Altering the rest interval during high‐intensity interval training does not affect muscle or performance adaptations
Publisher: Wiley
Date: 09-10-2012
DOI: 10.1113/EXPPHYSIOL.2012.067603
Abstract: It has been hypothesized that exercise-induced changes in metabolites and ions are crucial in the adaptation of contracting muscle. We tested this hypothesis by comparing adaptations to two different interval-training protocols (differing only in the rest duration between intervals), which provoked different perturbations in muscle metabolites and acid-base status. Prior to and immediately after training, 12 women performed the following tests: (1) a graded exercise test to determine peak oxygen uptake (V(O2)) (2) a high-intensity exercise bout (followed 60 s later by a repeated-sprint-ability test and (3) a repeat of the high-intensity exercise bout alone with muscle biopsies pre-exercise, immediately postexercise and after 60 s of recovery. Subjects performed 5 weeks (3 days per week) of training, with either a short (1 min HIT-1) or a long rest period (3 min HIT-3) between intervals training intensity and volume were matched. Muscle [H(+)] (155 ± 15 versus 125 ± 8 nmol l(-1) P < 0.05) and muscle lactate content (84.2 ± 7.9 versus 46.9 ± 3.1 mmol (g wet weight)(-1)) were both higher after HIT-1, while muscle phosphocreatine (PCr) content (52.8 ± 8.3 versus 63.4 ± 9.8 mmol (g wet weight)(-1)) was lower. There were no significant differences between the two groups regarding the increases in , repeated-sprint performance or muscle Na(+),K(+)-ATPase content. Following training, both groups had a significant decrease in postexercise muscle [H(+)] and lactate content, but not postexercise ATP or PCr. Postexercise PCr resynthesis increased following both training methods. In conclusion, intense interval training results in marked improvements in muscle Na(+),K(+)-ATPase content, PCr resynthesis and . However, manipulation of the rest period during intense interval training did not affect these changes.
Genetics and Sprint, Strength, and Power Performance
Publisher: Elsevier
Date: 2019
Mitochondrial respiration variability and simulations in human skeletal muscle: The Gene SMART study.
Publisher: Wiley
Date: 09-01-2020
IL6 (-174) and TNFA (-308) promoter polymorphisms are associated with systemic creatine kinase response to eccentric exercise
Publisher: Springer Science and Business Media LLC
Date: 30-08-2008
DOI: 10.1007/S00421-008-0728-4
Abstract: Exertional rhabdomyolysis is a complex and poorly understood entity. The inflammatory system has an important role in muscle injury and repair. Serum creatine kinase (CK) is often used as systemic biomarker representing muscle damage. Considerable variation exists in CK response between different subjects. Genetic elements may act as predisposition factors for exertional rhabdomyolysis. Based on their biological activity, we hypothesized that in healthy subjects IL6 G-174C and TNFA G-308A promoter polymorphisms would be associated with CK response to exercise. We determined serum CK activity pre- and post-maximal eccentric contractions of the elbow flexor muscles. IL6 G-174C and TNFA G-308A genotypes were analyzed for possible relationship with changes in serum CK activity. IL6 G-174C genotype was associated with CK activity in a dose-dependent fashion. Subjects with one or more of the -174C allele had a greater increase and higher peak CK values than subjects homozygous for the G allele (mean +/- SE U/L: GG, 2,604 +/- 821 GC, 7,592 +/- 1,111 CC, 8,403 +/- 3,849, ANOVA P = 0.0003 for GG + GC genotypes versus CC genotype, P = 0.0005 for linear trend). IL6-174CC genotype was associated with a greater than threefold increased risk of massive CK response (adjusted odds ratio 3.29, 95% confidence interval 1.27-7.85, P = 0.009). A milder association (P = 0.06) was noted between TNFA G-308A genotype and CK activity. In conclusion, we found a strong association of the IL6 G-174C genotype with systemic CK response to strenuous exercise. Data suggest that homozygosity for the IL6-174C allele is a clinically important risk factor for exercise-induced muscle injury, further supporting the central role of cytokines in the reactive inflammatory process of muscle damage and repair.
An epigenetic clock for human skeletal muscle
Publisher: Wiley
Date: 17-02-2020
DOI: 10.1002/JCSM.12556
No association between ACTN3 R577X and ACE I/D polymorphisms and endurance running times in 698 Caucasian athletes
Publisher: Springer Science and Business Media LLC
Date: 03-01-2018
ACTN3 R577X polymorphism and team-sport performance: A study involving three European cohorts
Publisher: Elsevier BV
Date: 2014
DOI: 10.1016/J.JSAMS.2013.02.005
Abstract: To determine the association between the α-actinin-3 (ACTN3) R577X polymorphism and elite team-sport athletic status in three cohorts of European team-sport athletes. We compared the genotype and allele frequencies of the ACTN3 R577X (rs1815739) polymorphisms between team-sport athletes (n=205), endurance athletes (n=305), sprint ower athletes (n=378), and non-athletic controls (n=568) from Poland, Russia and Spain all participants were unrelated European men. Genomic DNA was extracted from either buccal epithelium or peripheral blood using a standard protocol. Genotyping was performed using several methods, and the results were replicated following recent recommendations for genotype-phenotype association studies. Genotype distributions of all control and athletic groups met Hardy-Weinberg equilibrium (all p>0.05). Team-sport athletes were less likely to have the 577RR genotype compared to the 577XX genotype than sprint ower athletes [odds ratio: 0.58, 95% confidence interval: 0.34-0.39, p=0.045]. However, the ACTN3 R577X polymorphism was not associated with team-sports athletic status, compared to endurance athletes and non-athletic controls. Furthermore, no association was observed for any of the genotypes with respect to the level of competition (elite vs. national level). The ACTN3 R577X polymorphism was not associated with team-sport athletic status, compared to endurance athletes and non-athletic controls, and the observation that the 577RR genotype is overrepresented in power/sprint athletes compared with team-sport athletes needs to be confirmed in future studies.
Exercise training and DNA methylation in humans
Publisher: Wiley
Date: 19-11-2015
DOI: 10.1111/APHA.12414
Abstract: The response to exercise training (trainability) has been shown to have a strong heritable component. There is growing evidence suggesting that traits such as trainability do not only depend on the genetic code, but also on epigenetic signals. Epigenetic signals play an important role in the modulation of gene expression, through mechanisms such as DNA methylation and histone modifications. There is an emerging evidence to show that physical activity influences DNA methylation in humans. The present review aims to summarize current knowledge on the link between DNA methylation and physical activity in humans. We have critically reviewed the literature and only papers focused on physical activity and its influence on DNA methylation status were included a total of 25 papers were selected. We concluded that both acute and chronic exercises significantly impact DNA methylation, in a highly tissue- and gene-specific manner. This review also provides insights into the molecular mechanisms of exercise-induced DNA methylation changes, and recommendations for future research.
Uncovering the Bone-Muscle Interaction and Its Implications for the Health and Function of Older Adults (the Wellderly Project): Protocol for a Randomized Controlled Crossover Trial
Publisher: JMIR Publications Inc.
Date: 09-04-2021
DOI: 10.2196/18777
Abstract: Bone and muscle are closely linked anatomically, biochemically, and metabolically. Acute exercise affects both bone and muscle, implying a crosstalk between the two systems. However, how these two systems communicate is still largely unknown. We will explore the role of undercarboxylated osteocalcin (ucOC) in this crosstalk. ucOC is involved in glucose metabolism and has a potential role in muscle maintenance and metabolism. The proposed trial will determine if circulating ucOC levels in older adults at baseline and following acute exercise are associated with parameters of muscle function and if the ucOC response to exercise varies between older adults with low muscle quality and those with normal or high muscle quality. A total of 54 men and women aged 60 years or older with no history of diabetes and warfarin and vitamin K use will be recruited. Screening tests will be performed, including those for functional, anthropometric, and clinical presentation. On the basis of muscle quality, a combined equation of lean mass (leg appendicular skeletal muscle mass in kg) and strength (leg press one-repetition maximum), participants will be stratified into a high or low muscle function group and randomized into the controlled crossover acute intervention. Three visits will be performed approximately 7 days apart, and acute aerobic exercise, acute resistance exercise, and a control session (rest) will be completed in any order. Our primary outcome for this study is the effect of acute exercise on ucOC in older adults with low muscle function and those with high muscle function. The trial is active and ongoing. Recruitment began in February 2018, and 38 participants have completed the study as of May 26, 2019. This study will provide novel insights into bone and muscle crosstalk in older adults, potentially identifying new clinical biomarkers and mechanistic targets for drug treatments for sarcopenia and other related musculoskeletal conditions. Australia New Zealand Clinical Trials Registry ACTRN12618001756213 www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=375925. DERR1-10.2196/18777
Association Between MCT1 A1470T Polymorphism and Fat-Free Mass in Well-Trained Young Soccer Players
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2016
Nature versus Nurture in Determining Athletic Ability
Publisher: S. Karger AG
Date: 2016
DOI: 10.1159/000445238
Abstract: This overview provides a general discussion of the roles of nature and nurture in determining human athletic ability. On the nature (genetics) side, a review is provided with emphasis on the historical research and on several areas which are likely to be important for future research, including next-generation sequencing technologies. In addition, a number of well-designed training studies that could possibly reveal the biological mechanism ('cause') behind the association between gene variants and athletic ability are discussed. On the nurture (environment) side, we discuss common environmental variables including deliberate practice, family support, and the birthplace effect, which may be important in becoming an elite athlete. Developmental effects are difficult to disassociate with genetic effects, because the early life environment may have long-lasting effects in adulthood. With this in mind, the fetal programming hypothesis is also briefly reviewed, as fetal programming provides an excellent ex le of how the environment interacts with genetics. We conclude that the traditional argument of nature versus nurture is no longer relevant, as it has been clearly established that both are important factors in the road to becoming an elite athlete. With the availability of the next-generation genetics (sequencing) techniques, it is hoped that future studies will reveal the relevant genes influencing performance, as well as the interaction between those genes and environmental (nurture) factors.
Direct-to-consumer genetic testing for predicting sports performance and talent identification: Consensus statement
Publisher: BMJ
Date: 18-11-2015
Exercise is associated with younger methylome and transcriptome profiles in human skeletal muscle
Publisher: Cold Spring Harbor Laboratory
Date: 29-12-2022
DOI: 10.1101/2022.12.27.522062
Abstract: Exercise training prevents age-related decline in muscle function. Targeting epigenetic aging is a promising actionable mechanism and late-life exercise mitigates epigenetic aging in rodent muscle. Whether exercise training can decelerate, or reverse epigenetic aging in humans is unknown. Here, we performed a powerful meta-analysis of the methylome and transcriptome of an unprecedented number of human skeletal muscle s les (n = 3,176). We show that: 1) in iduals with higher baseline aerobic fitness have younger epigenetic and transcriptomic profiles, 2) exercise training leads to significant shifts of epigenetic and transcriptomic patterns towards a younger profile, and 3) muscle disuse “ages” the transcriptome. Higher fitness levels were associated with attenuated differential methylation and transcription during aging. Furthermore, both epigenetic and transcriptomic profiles shifted towards a younger state after exercise training interventions, while the transcriptome shifted towards an older state after forced muscle disuse. We demonstrate that exercise training targets many of the age-related transcripts and DNA methylation loci to maintain younger methylome and transcriptome profiles, specifically in genes related to muscle structure, metabolism and mitochondrial function. Our comprehensive analysis will inform future studies aiming to identify the best combination of therapeutics and exercise regimes to optimize longevity.
Optimal health and function among the elderly: lessening severity of ADL disability
Publisher: Springer Science and Business Media LLC
Date: 28-03-2009
DOI: 10.1007/S11556-009-0048-7
Abstract: Despite mounting evidence implicating sedentary behavior as a significant risk factor among the elderly, there is a limited amount of information on the type and amount of activity needed to promote optimal health and function in older people. Overall muscle strength and mass decline 30–50% between the ages of 30 and 80. The loss of muscle mass accounts for most of the observed loss of strength. The loss of muscle tissue is due to a decrease in the number of muscle fibers and to atrophy of the type II muscle fibers. The declining strength reduces the capacity to carry out basic activities of daily life and puts people at risk for falls and dependence on others. The objective of the present review is to examine the role of exercise training as a primary tool for increasing cardiopulmonary and muscular fitness in order to lessen the severity of disability in activities of daily living and to attain optimal health and functioning among the elderly.
Circulating osteoprogenitor (COP) cells have a mixed immune and mesenchymal progenitor function in humans
Publisher: Oxford University Press (OUP)
Date: 23-08-2023
Abstract: Circulating osteoprogenitors (COP) are a population of cells in the peripheral circulation that possess functional and phenotypical characteristics of multipotent stromal cells (MSCs). This population has a solid potential to become an abundant, accessible, and replenishable source of MSCs with multiple potential clinical applications. However, a comprehensive functional characterization of COP cells is still required to test and fully develop their use in clinical settings. This study characterized COP cells by comparing them to bone marrow-derived MSCs (BM-MSCs) and adipose-derived MSCs (ASCs) through detailed transcriptomic and proteomic analyses. We demonstrate that COP cells have a distinct gene and protein expression pattern with a significantly stronger immune footprint, likely owing to their hematopoietic lineage. In addition, regarding progenitor cell differentiation and proliferation pathways, COP cells have a similar expression pattern to BM-MSCs and ASCs. COP cells are a unique but functionally similar population to BM-MSCs and ASCs, sharing their proliferation and differentiation capacity, thus presenting an accessible source of MSCs with strong potential for translational regenerative medicine strategies.
Skeletal muscle methylome and transcriptome integration reveals profound sex differences related to muscle function and substrate metabolism
Publisher: Springer Science and Business Media LLC
Date: 03-11-2021
DOI: 10.1186/S13148-021-01188-1
Abstract: Nearly all human complex traits and diseases exhibit some degree of sex differences, with epigenetics being one of the main contributing factors. Various tissues display sex differences in DNA methylation however, this has not yet been explored in skeletal muscle, despite skeletal muscle being among the tissues with the most transcriptomic sex differences. For the first time, we investigated the effect of sex on autosomal DNA methylation in human skeletal muscle across three independent cohorts (Gene SMART, FUSION, and GSE38291) using a meta-analysis approach, totalling 369 human muscle s les (222 males and 147 females), and integrated this with known sex-biased transcriptomics. We found 10,240 differentially methylated regions (DMRs) at FDR 0.005, 94% of which were hypomethylated in males, and gene set enrichment analysis revealed that differentially methylated genes were involved in muscle contraction and substrate metabolism. We then investigated biological factors underlying DNA methylation sex differences and found that circulating hormones were not associated with differential methylation at sex-biased DNA methylation loci however, these sex-specific loci were enriched for binding sites of hormone-related transcription factors (with top TFs including androgen ( AR ), estrogen ( ESR1 ), and glucocorticoid ( NR3C1 ) receptors). Fibre type proportions were associated with differential methylation across the genome, as well as across 16% of sex-biased DNA methylation loci (FDR 0.005). Integration of DNA methylomic results with transcriptomic data from the GTEx database and the FUSION cohort revealed 326 autosomal genes that display sex differences at both the epigenome and transcriptome levels. Importantly, transcriptional sex-biased genes were overrepresented among epigenetic sex-biased genes ( p value = 4.6e−13), suggesting differential DNA methylation and gene expression between male and female muscle are functionally linked. Finally, we validated expression of three genes with large effect sizes ( FOXO3A , ALDH1A1 , and GGT7 ) in the Gene SMART cohort with qPCR. GGT7 , involved in antioxidant metabolism, displays male-biased expression as well as lower methylation in males across the three cohorts. In conclusion, we uncovered 8420 genes that exhibit DNA methylation differences between males and females in human skeletal muscle that may modulate mechanisms controlling muscle metabolism and health.
The gene SMART study: Method, study design, and preliminary findings
Publisher: Springer Science and Business Media LLC
Date: 11-2017
An epigenetic clock for human skeletal muscle
Publisher: Cold Spring Harbor Laboratory
Date: 11-11-2019
DOI: 10.1101/821009
Abstract: Ageing is associated with DNA methylation changes in all human tissues, and epigenetic markers can estimate chronological age based on DNA methylation patterns across tissues. However, the construction of the original pan-tissue epigenetic clock did not include skeletal muscle s les, and hence exhibited a strong deviation between DNA methylation and chronological age in this tissue. To address this, we developed a more accurate, muscle-specific epigenetic clock based on the genome-wide DNA methylation data of 682 skeletal muscle s les from 12 independent datasets (18-89 years old, 22% women, 99% Caucasian), all generated with Illumina HumanMethylation arrays (HM27, HM450 or HMEPIC). We also took advantage of the large number of s les to conduct an epigenome-wide association study (EWAS) of age-associated DNA methylation patterns in skeletal muscle. The newly developed clock uses 200 CpGs to estimate chronological age in skeletal muscle, 16 of which are in common with the 353 CpGs of the pan-tissue clock. The muscle clock outperformed the pan-tissue clock, with a median error of only 4.6 years across datasets ( vs 13.1 years for the pan-tissue clock, p 0.0001) and an average correlation of ρ = 0.62 between actual and predicted age across datasets ( vs ρ = 0.51 for the pan-tissue clock). Lastly, we identified 180 differentially methylated regions (DMRs) with age in skeletal muscle at a False Discovery Rate 0.005. However, Gene Set Enrichment Analysis did not reveal any enrichment for Gene Ontologies. We have developed a muscle-specific epigenetic clock that predicts age with better accuracy than the pan-tissue clock. We implemented the muscle clock in an R package called MEAT available on Bioconductor to estimate epigenetic age in skeletal muscle s les. This clock may prove valuable in assessing the impact of environmental factors, such as exercise and diet, on muscle-specific biological ageing processes.
Using genetic tests for talent identification in sports: too soon to be true
Publisher: Walter de Gruyter GmbH
Date: 2011
ACE ID genotype affects blood creatine kinase response to eccentric exercise
Publisher: American Physiological Society
Date: 12-2007
DOI: 10.1152/JAPPLPHYSIOL.00867.2007
Abstract: Unaccustomed exercise may cause muscle breakdown with marked increase in serum creatine kinase (CK) activity. The skeletal muscle renin-angiotensin system (RAS) plays an important role in exercise metabolism and tissue injury. A functional insertion ( I)/deletion ( D) polymorphism in the angiotensin I-converting enzyme ( ACE) gene (rs4646994) has been associated with ACE activity. We hypothesized that ACE ID genotype may contribute to the wide variability in in iduals' CK response to a given exercise. Young in iduals performed maximal eccentric contractions of the elbow flexor muscles. Pre- and postexercise CK activity was determined. ACE genotype was significantly associated with postexercise CK increase and peak CK activity. In iduals harboring one or more of the I allele had a greater increase and higher peak CK values than in iduals with the DD genotype. This response was dose-dependent (mean ± SE U/L: II, 8,882 ± 2,362 ID, 4,454 ± 1,105 DD, 2,937 ± 753, ANOVA, P = 0.02 P = 0.009 for linear trend). Multivariate stepwise regression analysis, which included age, sex, body mass index, and genotype subtypes, revealed that ACE genotype was the most powerful independent determinant of peak CK activity (adjusted odds ratio 1.3, 95% confidence interval 1.03–1.64, P = 0.02). In conclusion, we indicate a positive association of the ACE ID genotype with CK response to strenuous exercise. We suggest that the II genotype imposes increased risk for developing muscle damage, whereas the DD genotype may have protective effects. These findings support the role of local RAS in the regulation of exertional muscle injury.
Athlome Project Consortium: a concerted effort to discover genomic and other “omic” markers of athletic performance
Publisher: American Physiological Society
Date: 03-2016
DOI: 10.1152/PHYSIOLGENOMICS.00105.2015
Abstract: Despite numerous attempts to discover genetic variants associated with elite athletic performance, injury predisposition, and elite/world-class athletic status, there has been limited progress to date. Past reliance on candidate gene studies predominantly focusing on genotyping a limited number of single nucleotide polymorphisms or the insertion/deletion variants in small, often heterogeneous cohorts (i.e., made up of athletes of quite different sport specialties) have not generated the kind of results that could offer solid opportunities to bridge the gap between basic research in exercise sciences and deliverables in biomedicine. A retrospective view of genetic association studies with complex disease traits indicates that transition to hypothesis-free genome-wide approaches will be more fruitful. In studies of complex disease, it is well recognized that the magnitude of genetic association is often smaller than initially anticipated, and, as such, large s le sizes are required to identify the gene effects robustly. A symposium was held in Athens and on the Greek island of Santorini from 14–17 May 2015 to review the main findings in exercise genetics and genomics and to explore promising trends and possibilities. The symposium also offered a forum for the development of a position stand (the Santorini Declaration). Among the participants, many were involved in ongoing collaborative studies (e.g., ELITE, GAMES, Gene SMART, GENESIS, and POWERGENE). A consensus emerged among participants that it would be advantageous to bring together all current studies and those recently launched into one new large collaborative initiative, which was subsequently named the Athlome Project Consortium.
Sensitivity of the present-day climate to freshwater forcing associated with Antarctic Sea ice loss
Publisher: American Meteorological Society
Date: 08-2008
Abstract: The role played by Southern Hemisphere sea ice in the global climate system is explored using an earth system climate model of intermediate complexity. An ensemble of experiments is analyzed in which freshwater forcing equivalent to a complete 100-yr meltback of Southern Hemisphere sea ice is applied to a model run that simulates the present climate. This freshwater forcing acts to mildy subdue Southern Ocean deep overturning, reducing mean Antarctic Bottom Water (AABW) export by 0.5 Sv (1 Sv ≡ 106 m3 s−1) in the ensemble average. The decreased convective overturning cools the surface waters, thereby increasing sea ice volume and thus forming a negative feedback that stabilizes Antarctic sea ice. In contrast, the reduced convective overturn warms subsurface waters in the Southern Ocean, which, combined with the imposed freshening, results in a reduction in the meridional steric height gradient and hence a slowdown of the Antarctic Circumpolar Current (ACC). The reduction in ACC strength is, however, only modest at 1.5 Sv. These responses are thus of only weak magnitude, and the system recovers to its original state over time scales of decades. An extreme scenario experiment with essentially instantaneous addition of this meltwater load shows similar results, indicating the limited response of the climate system to the freshening implied by Antarctic sea ice melt. An additional experiment in which a much larger freshwater forcing of approximately 0.4 Sv is applied over 100 yr confirms the relatively weak response of the model’s climate state to such forcing, relative to the well-documented climatic effects of freshwater forcing added to the North Atlantic.
TheAMPD1C34T mutation is not associated with the status of Israeli athletes
Publisher: Informa UK Limited
Date: 05-2012
The Effect of Long-Term β-Adrenergic Receptor Blockade on the Oxygen Delivery and Extraction Relationship in Patients With Coronary Artery Disease
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2008
A human knockout model to investigate the influence of the α-actinin-3 protein on exercise-induced mitochondrial adaptations.
Publisher: Springer Science and Business Media LLC
Date: 03-09-2019
DOI: 10.1038/S41598-019-49042-Y
Abstract: Research in α-actinin-3 knockout mice suggests a novel role for α-actinin-3 as a mediator of cell signalling. We took advantage of naturally-occurring human “knockouts” (lacking α-actinin-3 protein) to investigate the consequences of α-actinin-3 deficiency on exercise-induced changes in mitochondrial-related genes and proteins, as well as endurance training adaptations. At baseline, we observed a compensatory increase of α-actinin-2 protein in ACTN3 XX (α-actinin-3 deficient n = 18) vs ACTN3 RR (expressing α-actinin-3 n = 19) participants but no differences between genotypes for markers of aerobic fitness or mitochondrial content and function. There was a main effect of genotype, without an interaction, for RCAN1-4 protein content (a marker of calcineurin activity). However, there was no effect of genotype on exercise-induced expression of genes associated with mitochondrial biogenesis, nor post-training physiological changes. In contrast to results in mice, loss of α-actinin-3 is not associated with higher baseline endurance-related phenotypes, or greater adaptations to endurance exercise training in humans.
Is the −174 C/G polymorphism of theIL6gene associated with elite power performance? A replication study with two different Caucasian cohorts
Publisher: Wiley
Date: 10-12-2010
DOI: 10.1113/EXPPHYSIOL.2010.055442
Abstract: A functional -174 C/G polymorphism in the interleukin-6 gene (IL6) is a candidate to explain in idual variations in exercise-related phenotypes. To replicate recent findings showing an association between the G allele and GG genotype of elite power sports performance in European (Spanish) Caucasian males, we compared allelic and genotypic frequencies of the IL6 -174 C/G polymorphism among elite endurance athletes (n = 74) and power athletes (n = 81) and non-athletic control subjects (n = 205) of both sexes from Israel. All subjects were Israeli Caucasians (with an equivalent ratio of non-Ashkenazi and Ashkenazi descent in each group 2:1). We found no differences in the genotype or allele frequencies among groups (all P > 0.3). We further compared the genotype and allele frequencies between national- (n = 109) and international-level Israeli athletes (n = 46) in the endurance and power group, and found no significant genotype or allele differences after adjusting for multiple comparisons. We repeated all the analyses after pooling the Israeli and Spanish control subjects, endurance and power elite athletes, and found no genotypic and allelic differences among groups. The results did not change when the analyses were repeated including only the best Israeli athletes (i.e. the international-level group) together with the group of elite Spanish athletes (P > 0.2). In conclusion, the results of the present study did not show an association between the G allele of the IL6 -174 G/C polymorphism and power sports performance in the Israeli (Caucasian) population. Our findings support the need to replicate association results between genetic polymorphisms and athletic status in populations of different ethnic backgrounds with the largest possible population s les.
Interaction between SNPs in the NRF2 gene and elite endurance performance
Publisher: American Physiological Society
Date: 03-2010
DOI: 10.1152/PHYSIOLGENOMICS.00199.2009
Abstract: Nuclear respiratory factor 2 (NRF2), a member of the Cap-N-Collar family of transcription factors, plays an important role in the mitochondrial biogenesis, and variants of NRF2 gene have been associated with endurance performance. The aims of the present study were 1) to compare NRF2 A/C (rs12594956) and NRF2 C/T (rs8031031) genotype and allele frequencies between athletes of sports with different demands (endurance vs. sprinters) as well as between competitive levels (elite level vs. national level) and 2) to analyze the interaction of these two polymorphisms and its influence on the level of endurance performance. One hundred and fifty-five track and field athletes (74 endurance athletes and 81 sprinters) and 240 nonathletic healthy in iduals participated in this study. Endurance athletes presented a higher frequency of the AA (rs12594956) and CT (rs8031031) genotypes than sprinters and the control group, as well as higher A and T alleles, respectively. These differences did not appear between the sprinters and control subjects. The odds ratio for harboring the “optimal genotype” ( NRF2 AA+ NRF2 CT) was 4.53 (95% confidence interval 1.23–16.6) in the whole cohort of endurance athletes and 6.55 (95% confidence interval 1.12–38.25) in elite-level endurance athletes, compared with control subjects and both levels of sprinters. In conclusion, our data indicate that the NRF2 A/C and NRF2 C/T single nucleotide polymorphisms (SNPs) are associated, separately and in combination, with elite endurance athletes, which supports the notion that these specific gene variants might belong to a growing group of SNPs that are associated with endurance performance.
Short-Term Intensified Cycle Training Alters Acute and Chronic Responses of PGC1α and Cytochrome C Oxidase IV to Exercise in Human Skeletal Muscle
Publisher: Public Library of Science (PLoS)
Date: 28-12-2012
Can we optimise the exercise training prescription to maximise improvements in mitochondria function and content?
Publisher: Elsevier BV
Date: 04-2014
DOI: 10.1016/J.BBAGEN.2013.10.012
Abstract: While there is agreement that exercise is a powerful stimulus to increase both mitochondrial function and content, we do not know the optimal training stimulus to maximise improvements in mitochondrial biogenesis. This review will focus predominantly on the effects of exercise on mitochondrial function and content, as there is a greater volume of published research on these adaptations and stronger conclusions can be made. The results of cross-sectional studies, as well as training studies involving rats and humans, suggest that training intensity may be an important determinant of improvements in mitochondrial function (as determined by mitochondrial respiration), but not mitochondrial content (as assessed by citrate synthase activity). In contrast, it appears that training volume, rather than training intensity, may be an important determinant of exercise-induced improvements in mitochondrial content. Exercise-induced mitochondrial adaptations are quickly reversed following a reduction or cessation of physical activity, highlighting that skeletal muscle is a remarkably plastic tissue. Due to the small number of studies, more research is required to verify the trends highlighted in this review, and further studies are required to investigate the effects of different types of training on the mitochondrial sub-populations and also mitochondrial adaptations in different fibre types. Further research is also required to better understand how genetic variants influence the large in idual variability for exercise-induced changes in mitochondrial biogenesis. The importance of mitochondria for both athletic performance and health underlines the importance of better understanding the factors that regulate exercise-induced changes in mitochondrial biogenesis. This article is part of a Special Issue entitled Frontiers of Mitochondrial Research.
ACTN3 R577X Gene Variant Is Associated With Muscle-Related Phenotypes in Elite Chinese Sprint/Power Athletes
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2017
DOI: 10.1519/JSC.0000000000001558
Abstract: Yang, R, Shen, X, Wang, Y, Voisin, S, Cai, G, Fu, Y, Xu, W, Eynon, N, Bishop, DJ, and Yan, X. ACTN3 R577X gene variant is associated with muscle-related phenotypes in elite Chinese sprint ower athletes. J Strength Cond Res 31(4): 1107–1115, 2017—The ACTN3 R577X polymorphism (rs1815739) has been shown to influence athletic performance. The aim of this study was to investigate the prevalence of this polymorphism in elite Chinese track and field athletes, and to explore its effects on athletes' level of competition and lower-extremity power. We compared the ACTN3 R577X genotypes and allele frequencies in 59 elite sprint ower athletes, 44 elite endurance athletes, and 50 healthy controls from Chinese Han origin. We then subcategorized the athletes into international level and national level and investigated the effects of ACTN3 genotype on lower-extremity power. Genotype distribution of the sprint ower athletes was significantly different from endurance athletes ( p = 0.001) and controls ( p 0.001). The frequency of the RR genotype was significantly higher in international-level than that in the national-level sprint ower athletes ( p = 0.004), with no international-level sprint ower athletes with XX genotype. The best standing long jump and standing vertical jump results of sprint ower athletes were better in the RR than those in the RX + XX genotypes ( p = 0.004 and p = 0.001, respectively). In conclusion, the ACTN3 R577X polymorphism influences the level of competition and lower-extremity power of elite Chinese sprint ower athletes. Including relevant phenotypes such as muscle performance in future studies is important to further understand the effects of gene variants on elite athletic performance.
Implementation of multiple statistical methods to estimate variability and individual response to training
Publisher: Informa UK Limited
Date: 27-03-2023
DOI: 10.1080/17461391.2022.2048894
Abstract: Multiple statistical methods have been proposed to estimate in idual responses to exercise training yet, the evaluation of these methods is lacking. We compared five of these methods including the following: the use of a control group, a control period, repeated testing during an intervention, a reliability trial and a repeated intervention. Apparently healthy males from the Gene SMART study completed a 4-week control period, 4 weeks of High-Intensity Interval Training (HIIT), >1 year of washout, and then subsequently repeated the same 4 weeks of HIIT, followed by an additional 8 weeks of HIIT. Aerobic fitness measurements were measured in duplicates at each time point. We found that the control group and control period were not intended to measure the degree to which in iduals responded to training, but rather estimated whether in idual responses to training can be detected with the current exercise protocol. After a repeated intervention, in idual responses to 4 weeks of HIIT were not consistent, whereas repeated testing during the 12-week-long intervention was able to capture in idual responses to HIIT. The reliability trial should not be used to study in idual responses, rather should be used to classify participants as responders with a certain level of confidence. 12 weeks of HIIT with repeated testing during the intervention is sufficient and cost-effective to measure in idual responses to exercise training since it allows for a confident estimate of an in idual's true response. Our study has significant implications for how to improve the design of exercise studies to accurately estimate in idual responses to exercise training interventions. HighlightsWhat are the findings?We implemented five statistical methods in a single study to estimate the magnitude of within-subject variability and quantify responses to exercise training at the in idual level.The various proposed methods used to estimate in idual responses to training provide different types of information and rely on different assumptions that are difficult to test.Within-subject variability is often large in magnitude, and as such, should be systematically evaluated and carefully considered in future studies to successfully estimate in idual responses to training.
ACTN3R577X Polymorphism and Israeli Top-level Athletes
Publisher: Georg Thieme Verlag KG
Date: 18-06-2009
Abstract: A common genetic variation in the alpha-actinin-3 ( ACTN3) gene causes a replacement of an arginine (R) with a premature stop codon (X) at amino-acid 577 (rs1815739). While the R allele has been found to be associated with power-oriented performance, the XX genotype may be linked with endurance ability. To test this hypothesis, we studied the distribution of ACTN3 genotypes in 155 Israeli athletes (age=35.9+12.2 years) classified by sport (endurance runners and sprinters) and in 240 sedentary in iduals. The sprinters' allele frequencies (AF: R/X=0.7/0.3) and 577RR genotype distribution percentage (GD: RR=52%) differed markedly from those of the endurance athletes (AF: R/X=0.53/0.47, p=0.000007 GD: RR=18%, p=0.00009) and the control group (AF: R/X=0.55/0.45, p=0.0002 GD: RR=27.3%, p=0.000003). A comparison between the top-level and national-level sprinters revealed that the R allele occurs more often in the top-level sprinters. A significantly higher proportion of the XX genotype was observed in endurance athletes (34%) compared with controls (18%, p=0.02) and sprinters (13%, p=0.002). However, top-level and national level endurance athletes had similar allele and genotype frequencies. We conclude that the ACTN3 R allele is associated with top-level sprint performance and the X allele and XX genotypes may not be critical but rather additive to endurance performance.
Genetic Contributions to Muscle Strength
Publisher: Routledge
Date: 14-03-2019
Making sense of the ageing methylome.
Publisher: Springer Science and Business Media LLC
Date: 02-05-2022
DOI: 10.1038/S41576-022-00477-6
Abstract: Over time, the human DNA methylation landscape accrues substantial damage, which has been associated with a broad range of age-related diseases, including cardiovascular disease and cancer. Various age-related DNA methylation changes have been described, including at the level of in idual CpGs, such as differential and variable methylation, and at the level of the whole methylome, including entropy and correlation networks. Here, we review these changes in the ageing methylome as well as the statistical tools that can be used to quantify them. We detail the evidence linking DNA methylation to ageing phenotypes and the longevity strategies aimed at altering both DNA methylation patterns and machinery to extend healthspan and lifespan. Lastly, we discuss theories on the mechanistic causes of epigenetic ageing.
Elite athletes’ genetic predisposition for altered risk of complex metabolic traits
Publisher: Springer Science and Business Media LLC
Date: 23-01-2015
Genetic variants associated with exercise performance in both moderately trained and highly trained individuals
Publisher: Springer Science and Business Media LLC
Date: 02-01-2020
DOI: 10.1007/S00438-019-01639-8
Abstract: Adaptation to exercise training is a complex trait that may be influenced by genetic variants. We identified 36 single nucleotide polymorphisms (SNPs) that had been previously associated with endurance or strength performance, exercise-related phenotypes or exercise intolerant disorders. A MassARRAY multiplex genotyping assay was designed to identify associations with these SNPs against collected endurance fitness phenotype parameters obtained from two exercise cohorts (Gene SMART study n = 58 and Hawaiian Ironman Triathlon 2008 n = 115). These parameters included peak power output (PP), a time trial (TT), lactate threshold (LT), maximal oxygen uptake (VO
MCT1 A1470T: A novel polymorphism for sprint performance?
Publisher: Elsevier BV
Date: 2015
DOI: 10.1016/J.JSAMS.2013.12.008
Abstract: The A1470T polymorphism (rs1049434) in the monocarboxylate (lactate yruvate) transporter 1 gene (MCT1) has been suggested to influence athletic performance in the general population. We compared genotype distributions and allele frequencies of the MCT1 gene A1470T polymorphism between endurance athletes, sprint ower athletes and matched controls. We also examined the association between the MCT1 A1470T and the athletes' competition level ('elite' and 'national' level). The study involved endurance athletes (n=112), sprint ower athletes (n=100), and unrelated sedentary controls (n=621), all Caucasians. Genomic DNA was extracted from buccal epithelium using a standard protocol. We conducted Fisher's exact tests and multinomial logistic regression analyses to assess the association between MCT1 genotype and athletic status/competition level. Sprint ower athletes were more likely than controls to possess the minor T allele (TT genotype compared to the AA [p<0.001] TT or AT compared to the AA [p=0.007] TT compared to both AA and AT genotypes [p<0.001]). Likewise, sprint ower athletes were more likely than endurance athletes to have the TT genotype compared to the AA (p=0.029) and the TT compared to both AA and AT genotypes (p=0.027). Furthermore, elite sprint ower athletes were more likely than national-level athletes to have the TT genotype compared to the AA (p=0.044), and more likely to have the TT genotype compared to both AA and AT genotypes (recessive model) (p=0.045). The MCT1 TT genotype is associated with elite sprint ower athletic status. Future studies are encouraged to replicate these findings in other elite athlete cohorts.
Is evolutionary loss our gain? The role of ACTN3 p.Arg577Ter (R577X) genotype in athletic performance, ageing, and disease
Publisher: Hindawi Limited
Date: 08-11-2018
DOI: 10.1002/HUMU.23663
Abstract: A common null polymorphism in the ACTN3 gene (rs1815739:C>T) results in replacement of an arginine (R) with a premature stop codon (X) at amino acid 577 in the fast muscle protein α-actinin-3. The ACTN3 p.Arg577Ter allele (aka p.R577* or R577X) has undergone positive selection, with an increase in the X allele frequency as modern humans migrated out of Africa into the colder, less species-rich Eurasian climates suggesting that the absence of α-actinin-3 may be beneficial in these conditions. Approximately 1.5 billion people worldwide are completely deficient in α-actinin-3. While the absence of α-actinin-3 influences skeletal muscle function and metabolism this does not result in overt muscle disease. α-Actinin-3 deficiency (ACTN3 XX genotype) is constantly underrepresented in sprint ower performance athletes. However, recent findings from our group and others suggest that the ACTN3 R577X genotype plays a role beyond athletic performance with effects observed in ageing, bone health, and inherited muscle disorders such as McArdle disease and Duchenne muscle dystrophy. In this review, we provide an update on the current knowledge regarding the influence of ACTN3 R577X on skeletal muscle function and its potential biological and clinical implications. We also outline future research directions to explore the role of α-actinin-3 in healthy and diseased populations.
Skeletal muscle methylome and transcriptome integration reveals profound sex differences related to muscle function and substrate metabolism
Publisher: Cold Spring Harbor Laboratory
Date: 17-03-2021
DOI: 10.1101/2021.03.16.435733
Abstract: Nearly all human complex traits and diseases exhibit some degree of sex differences, with epigenetics being one of the main contributing factors. Various tissues display sex differences in DNA methylation, however this has not yet been explored in skeletal muscle, despite skeletal muscle being among the tissues with the most transcriptomic sex differences. For the first time, we investigated the effect of sex on autosomal DNA methylation in human skeletal muscle across three independent cohorts (Gene SMART, FUSION, and GSE38291) using a meta-analysis approach, totalling 369 human muscle s les (222 males, 147 females), and integrated this with known sex-biased transcriptomics. We found 10,240 differentially methylated regions (DMRs) at FDR 0.005, 94% of which were hypomethylated in males, and gene set enrichment analysis revealed that differentially methylated genes were involved in muscle contraction and substrate metabolism. We then investigated biological factors underlying DNA methylation sex differences and found that circulating hormones were not associated with differential methylation at sex-biased DNA methylation loci, however these sex-specific loci were enriched for binding sites of hormone-related transcription factors (with top TFs including androgen ( AR ), estrogen ( ESR1 ), and glucocorticoid ( NR3C1 ) receptors). Fibre type proportions were associated with differential methylation across the genome, as well as across 16 % of sex-biased DNA methylation loci (FDR 0.005). Integration of DNA methylomic results with transcriptomic data from the GTEx database and the FUSION cohort revealed 326 autosomal genes that display sex differences at both the epigenome and transcriptome levels. Importantly, transcriptional sex-biased genes were overrepresented among epigenetic sex-biased genes (p-value = 4.6e-13), suggesting differential DNA methylation and gene expression between male and female muscle are functionally linked. Finally, we validated expression of three genes with large effect sizes ( FOXO3A, ALDH1A1 , and GGT7 ) in the Gene SMART cohort with qPCR. GGT7 , involved in antioxidant metabolism, displays male-biased expression as well as lower methylation in males across the three cohorts. In conclusion, we uncovered 8,420 genes that exhibit DNA methylation differences between males and females in human skeletal muscle that may modulate mechanisms controlling muscle metabolism and health. The importance of uncovering biological sex differences and their translation to physiology has become increasingly evident. Using a large-scale meta-analysis of three cohorts, we perform the first comparison of genome-wide skeletal muscle DNA methylation between males and females, and identify thousands of genes that display sex-differential methylation. We then explore intrinsic biological factors that may be underlying the DNA methylation sex differences, such as fibre type proportions and sex hormones. Leveraging the GTEx database, we identify hundreds of genes with both sex-differential expression and DNA methylation in skeletal muscle. We further confirm the sex-biased genes with gene expression data from two cohorts included in the methylation meta-analysis. Our study integrates genomewide sex-biased DNA methylation and expression in skeletal muscle, shedding light on distinct sex differences in skeletal muscle.
Influence of the MCT1 rs1049434 on Indirect Muscle Disorders/Injuries in Elite Football Players
Publisher: Springer Science and Business Media LLC
Date: 11-10-2015
Physiological and molecular sex differences in human skeletal muscle in response to exercise training
Publisher: Wiley
Date: 07-12-2021
DOI: 10.1113/JP279499
Abstract: Sex differences in exercise physiology, such as substrate metabolism and skeletal muscle fatigability, stem from inherent biological factors, including endogenous hormones and genetics. Studies investigating exercise physiology frequently include only males or do not take sex differences into consideration. Although there is still an underrepresentation of female participants in exercise research, existing studies have identified sex differences in physiological and molecular responses to exercise training. The observed sex differences in exercise physiology are underpinned by the sex chromosome complement, sex hormones and, on a molecular level, the epigenome and transcriptome. Future research in the field should aim to include both sexes, control for menstrual cycle factors, conduct large‐scale and ethnically erse studies, conduct meta‐analyses to consolidate findings from various studies, leverage unique cohorts (such as post‐menopausal, transgender, and those with sex chromosome abnormalities), as well as integrate tissue and cell‐specific ‐omics data. This knowledge is essential for developing deeper insight into sex‐specific physiological responses to exercise training, thus directing future exercise physiology studies and practical application. image
THE GSTP1 c.313A>G POLYMORPHISM MODULATES THE CARDIORESPIRATORY RESPONSE TO AEROBIC TRAINING
Publisher: Index Copernicus
Date: 12-09-2014
Genomics of elite sporting performance: what little we know and necessary advances
Publisher: BMJ
Date: 30-04-2013
DOI: 10.1136/BJSPORTS-2013-092400
Abstract: Numerous reports of genetic associations with performance-related phenotypes have been published over the past three decades but there has been limited progress in discovering and characterising the genetic contribution to elite/world-class performance, mainly owing to few coordinated research efforts involving major funding initiatives/consortia and the use primarily of the candidate gene analysis approach. It is timely that exercise genomics research has moved into a new era utilising well-phenotyped, large cohorts and genome-wide technologies--approaches that have begun to elucidate the genetic basis of other complex traits/diseases. This review summarises the most recent and significant findings from sports genetics and explores future trends and possibilities.
Resting Measures and Physiological Responses to Exercise for the Determination of Prognosis in Patients With Chronic Heart Failure
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2010
Activin A level is associated with physical function in critically ill patients
Publisher: Elsevier BV
Date: 09-2023
Identification of novel mitochondrial and mitochondrial related genetic loci associated with exercise response in the Gene SMART study
Publisher: Cold Spring Harbor Laboratory
Date: 20-02-2020
DOI: 10.1101/2020.02.20.957340
Abstract: Mitochondria supply intracellular energy requirements during exercise. Specific mitochondrial haplogroups and mitochondrial genetic variants have been associated with athletic performance, and exercise responses. However, these associations were discovered using underpowered, candidate gene approaches, and consequently have not been replicated. Here, we used whole-mitochondrial genome sequencing, in conjunction with high-throughput genotyping arrays, to discover novel genetic variants associated with exercise responses in the Gene SMART (Skeletal Muscle Adaptive Response to Training) cohort (n=62 completed). We performed a Principal Component Analysis of cohort aerobic fitness measures to build composite traits and test for variants associated with exercise outcomes. None of the mitochondrial genetic variants but nine nuclear encoded variants in eight separate genes were found to be associated with exercise responses (FDR .05) (rs11061368: DIABLO, rs113400963: FAM185A, rs6062129 and rs6121949: MTG2, rs7231304: AFG3L2, rs2041840: NDUFAF7, rs7085433: TIMM23, rs1063271: SPTLC2, rs2275273: ALDH18A1). Additionally, we outline potential mechanisms by which these variants may be contributing to exercise phenotypes. Our data suggest novel nuclear-encoded SNPs and mitochondrial pathways associated with exercise response phenotypes. Future studies should focus on validating these variants across different cohorts and ethnicities. Previous exercise genetic studies contain many flaws that impede the growth in knowledge surrounding change in exercise outcomes. In particular, exercise studies looking at mtDNA variants have looked at very small portions of the mitochondrial genome. Mitochondria are the ‘power house’ of the cell and therefore understanding the mitochondrial genetics behind adaptations to training can help us fill knowledge gaps in current research. Here, we utilised a new mitochondrial genetic sequencing technique to examine all mitochondrial and mitochondrial related genetic variations. We have shown that there were no mitochondrial specific variants that influenced exercise training however there were 9 related variants that were significantly associated with exercise phenotypes. Additionally, we have shown that building composite traits increased the significance of our association testing and lead to novel findings. We will be able to understand why response to training is so varied and increase the effectiveness of exercise training on a host of metabolic disorders.
The ACTN3 R577X Polymorphism across Three Groups of Elite Male European Athletes
Publisher: Public Library of Science (PLoS)
Date: 16-08-2012
ACTN3 R577X and ACE I/D gene variants influence performance in elite sprinters: a multi-cohort study
Publisher: Springer Science and Business Media LLC
Date: 13-04-2016
Gene variants within the COL1A1 gene are associated with reduced anterior cruciate ligament injury in professional soccer players
Publisher: Elsevier BV
Date: 09-2013
DOI: 10.1016/J.JSAMS.2012.10.004
Abstract: To examine the association of the COL1A1 -1997G/T and +1245G/T polymorphisms, in idually and as haplotypes, with anterior cruciate ligament ruptures in professional soccer players. Subjects were 91 male professional soccer players with surgically diagnosed primary anterior cruciate ligament ruptures. The control group consisted of 143 apparently healthy male professional soccer players, who were without any self-reported history of ligament or tendon injury. Both subjects and healthy controls are from the same soccer teams, of the same ethnicity (Polish, East-Europeans for ≥3 generations), a similar age category, and had a comparable level of exposure to anterior cruciate ligament injury. Genomic DNA was extracted from the oral epithelial cells using GenElute Mammalian Genomic DNA Miniprep Kit (Sigma, Germany). All s les were genotyped using a Rotor-Gene real-time polymerase chain reaction. Genotype distributions for both polymorphisms met the Hardy-Weinberg expectations in both subjects and controls (p>0.05). Higher frequency of the COL1A1 G-T (-1997G/T and +1245G/T polymorphisms) haplotype was significantly associated with reduced risk for anterior cruciate ligament rupture (Hap.score -1.98, p=0.048). The TT genotype was under-represented in the anterior cruciate ligament rupture group. However, this result was not statistically significant (p=0.084 Fisher's exact test, recessive mode: TT vs GT+GG). Higher frequency of the COL1A1 G-T haplotype is associated with reduced risk of anterior cruciate ligament injury in a group of professional soccer players. Consequently, carrying two copies the COL1A1 G-T haplotype may be protective against anterior cruciate ligament injury.
Uncovering the Bone-Muscle Interaction and Its Implications for the Health and Function of Older Adults (the Wellderly Project): Protocol for a Randomized Controlled Crossover Trial (Preprint)
Publisher: JMIR Publications Inc.
Date: 18-03-2020
Abstract: one and muscle are closely linked anatomically, biochemically, and metabolically. Acute exercise affects both bone and muscle, implying a crosstalk between the two systems. However, how these two systems communicate is still largely unknown. We will explore the role of undercarboxylated osteocalcin (ucOC) in this crosstalk. ucOC is involved in glucose metabolism and has a potential role in muscle maintenance and metabolism. he proposed trial will determine if circulating ucOC levels in older adults at baseline and following acute exercise are associated with parameters of muscle function and if the ucOC response to exercise varies between older adults with low muscle quality and those with normal or high muscle quality. total of 54 men and women aged 60 years or older with no history of diabetes and warfarin and vitamin K use will be recruited. Screening tests will be performed, including those for functional, anthropometric, and clinical presentation. On the basis of muscle quality, a combined equation of lean mass (leg appendicular skeletal muscle mass in kg) and strength (leg press one-repetition maximum), participants will be stratified into a high or low muscle function group and randomized into the controlled crossover acute intervention. Three visits will be performed approximately 7 days apart, and acute aerobic exercise, acute resistance exercise, and a control session (rest) will be completed in any order. Our primary outcome for this study is the effect of acute exercise on ucOC in older adults with low muscle function and those with high muscle function. he trial is active and ongoing. Recruitment began in February 2018, and 38 participants have completed the study as of May 26, 2019. his study will provide novel insights into bone and muscle crosstalk in older adults, potentially identifying new clinical biomarkers and mechanistic targets for drug treatments for sarcopenia and other related musculoskeletal conditions. ustralia New Zealand Clinical Trials Registry ACTRN12618001756213 www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=375925. ERR1-10.2196/18777
Statistical Considerations for Exercise Protocols Aimed at Measuring Trainability.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2019
DOI: 10.1249/JES.0000000000000176
Abstract: The in idual response to exercise training is of great interest with methods that have been proposed to measure this response reviewed in this paper. However, in idual training response estimates may be biased by various sources of variability present in exercise studies, and in particular by within-subject variability. We propose the use of protocols that can separate trainability from within-subject variability.
Osteocalcin and its forms across the lifespan in adult men
Publisher: Elsevier BV
Date: 2020
DOI: 10.1016/J.BONE.2019.115085
Abstract: Osteocalcin (OC), an osteoblast-specific secreted protein expressed by mature osteoblasts, is used in clinical practice and in research as a marker of bone turnover. The carboxylated (cOC) and undercarboxylated (ucOC) forms may have a different biological function but age-specific reference ranges for these components are not established. Given the different physiological roles, development of reference ranges may help to identify people at risk for bone disease. Blood was collected in the morning after an overnight fast from 236 adult men (18 to 92 years old) free of diabetes, antiresorptive, warfarin or glucocorticoid use. Serum was analyzed for total osteocalcin (tOC) and the ucOC fraction using the hydroxyapatite binding method. cOC, ucOC/tOC and cOC/tOC ratios were calculated. Reference intervals were established by polynomial quantile regression analysis. The normal ranges for young men (≤30 years) were: tOC 17.9-56.8 ng/mL, ucOC 7.1-22.0 ng/mL, cOC 8.51-40.3 ng/mL (2.5th to 97.5th quantiles). Aging was associated with a "U" shaped pattern for tOC, cOC and ucOC levels. ucOC/tOC ratio was higher, while cOC/tOC ratio was lower in men of advanced age. Age explained ∼31%, while body mass index explained ∼4%, of the variance in the ratios. We have defined normal reference ranges for the OC forms in Australian men and demonstrated that the OC ratios may be better measures, than the absolute values, to identify the age-related changes on OC in men. These ratios may be incorporated into future research and clinical trials, and their associations with prediction of events, such as fracture or diabetes risk, should be determined.
Genomic haplotype within the Peroxisome Proliferator-Activated Receptor Delta (PPARD) gene is associated with elite athletic status
Publisher: Wiley
Date: 14-10-2013
DOI: 10.1111/SMS.12126
Abstract: Peroxisome proliferator-activated receptor delta (PPARδ encoded by the PPARD gene) plays a role in energy metabolism and mitochondrial function. We have investigated the distribution of PPARD rs2267668, rs2016520 and rs1053049 polymorphisms, in idually and in haplotype, in a cohort of 660 elite athletes which was sub ided into four different groups based on the different metabolic demands of their respective sports and 704 healthy controls. PPARD rs2016529 and rs1053049 were in idually associated with overall elite athletic performance (P = 0.00002 and P = 0.0002) and also with athletes grouped as strength endurance (P = 0.00008 and P = 0.0003). Furthermore, PPARD A/C/C haplotype (rs2267668/rs2016520/rs1053049) was significantly underrepresented in all athletes and each subgroup of athletes when compared with controls (P < 0.000001), suggesting that harboring this specific haplotype is unfavorable for becoming an elite athlete. These results help to identify which genetic profiles may contribute to elite athletic performance, specifically the role of variants within the PPARD gene, and may be useful in talent identification or optimizing the response to training.
CK-MM Gene Polymorphism Does not Influence the Blood CK Activity Levels After Exhaustive Eccentric Exercise
Publisher: Georg Thieme Verlag KG
Date: 15-02-2010
Abstract: Gene variants, such as creatine kinase (CK) polymorphisms, have been suggested to explain the inter-in idual blood CK response to eccentric exercise. However, since this association is still doubtful, the purpose of this study was to analyse the relationship between the magnitudes of the CK response to exercise with the occurrence of muscle CK-MM NcoI polymorphism in young healthy subjects. Blood CK activity was assessed in 70 subjects immediately before and 3, 24, 48, 72, 96, 120, 168 h after strenuous eccentric exercise. Based on the amount of CK release by each subject, the s le was distributed in quartiles and the genotype and allele frequency distribution was compared among quartiles. Despite the inter-in idual variability of CK response observed between subjects, there were no differences in genotype and allele frequencies among quartiles. The results allowed us to conclude that CK response after exhaustive eccentric exercise is not associated with CK-MM Ncol polymorphism.
Genetic and epigenetic sex-specific adaptations to endurance exercise
Publisher: Informa UK Limited
Date: 13-04-2019
Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness
Publisher: Springer Science and Business Media LLC
Date: 12-07-2017
DOI: 10.1038/NCOMMS16015
Abstract: Hand grip strength is a widely used proxy of muscular fitness, a marker of frailty, and predictor of a range of morbidities and all-cause mortality. To investigate the genetic determinants of variation in grip strength, we perform a large-scale genetic discovery analysis in a combined s le of 195,180 in iduals and identify 16 loci associated with grip strength ( P × 10 −8 ) in combined analyses. A number of these loci contain genes implicated in structure and function of skeletal muscle fibres ( ACTG1 ), neuronal maintenance and signal transduction ( PEX14, TGFA, SYT1 ), or monogenic syndromes with involvement of psychomotor impairment ( PEX14, LRPPRC and KANSL1 ). Mendelian randomization analyses are consistent with a causal effect of higher genetically predicted grip strength on lower fracture risk. In conclusion, our findings provide new biological insight into the mechanistic underpinnings of grip strength and the causal role of muscular strength in age-related morbidities and mortality.
The response of circulating brain natriuretic peptide to academic stress in college students
Publisher: Informa UK Limited
Date: 2010
DOI: 10.3109/10253890902818357
Abstract: Brain natriuretic peptide (BNP), a cardiac peptide, has been implicated in the regulation of hypothalamic-pituitary-adrenocortical (HPA) responses to psychological stressors. The influence of academic stress on circulating concentration of the N-terminal fragment of BNP precursor (NT-proBNP), and in relation to the stress hormone (cortisol) response was studied in 170 college students undergoing major examinations. Just prior to the examination, we measured self-estimated stress level, systolic, and diastolic blood pressure (SBP, DBP), heart rate (HR), plasma levels of cortisol, and NT-proBNP. These parameters were compared to the participants' baseline measurements, taken at the same hour of a different 'control day', without a major examination to induce stress. Hemodynamic variables (SBP, DBP, and HR) increased on the examination day compared with baseline values ( p < 0.001). Circulating cortisol concentration increased before examinations (+42%, p < 0.001). The response to stress was marked by a significant decrease in plasma NT-proBNP concentration (-40%, p < 0.001). We found in males a significant interaction between the cortisol elevation with examination stress and the NT-proBNP reduction ( p = 0.02). In response to academic stress, the plasma cortisol elevation was accompanied by a marked reduction in plasma NT-proBNP level. These data may indicate that mental stress entails an interface between the HPA axis and the peripheral natriuretic peptide system, leading to reciprocating changes in circulating levels of the corresponding hormones.
Is there an interaction betweenPPARDT294C andPPARGC1AGly482Ser polymorphisms and human endurance performance?
Publisher: Wiley
Date: 14-10-2009
DOI: 10.1113/EXPPHYSIOL.2009.049668
Abstract: Functional Gly482Ser (rs8192678) and T294C (rs2016520) polymorphisms in the peroxisome proliferator-activated receptor gamma coactivator-1 (PPARGC1A) and peroxisome proliferator-activated receptor delta (PPARD) genes, respectively, have been associated with mRNA and/or protein activity. The aim of this study was to determine their frequency distribution among 155 Israeli athletes (endurance athletes and sprinters) and 240 healthy control subjects. There were no differences between the endurance athletes, the sprinters and the control group across the PPARD T294C genotypes (P = 0.62). Similarly, no statistical differences were found between the subgroups of elite-level endurance athletes (those who had represented Israel in a world track and field ch ionship or in the Olympic Games) and national-level endurance athletes (P = 0.3), or between elite-level and national-level sprinters (P = 0.9). However, a combined influence of these two polymorphisms on endurance performance was found. The PPARD CC + PPARGC1A Gly/Gly genotypes were more frequently found in the elite endurance athletes than in national-level endurance athletes (P < 0.000). In the cohort of endurance athletes, the odds ratio of the 'optimal genotype' for endurance athletes (PPARD CC + PPARGC1A Gly/Gly + PPARGC1A Gly/Ser) being an elite-level athlete was 8.32 (95% confidence interval 2.2-31.4). In conclusion, the present study suggests that PPARD T294C is not associated with endurance performance. However, a higher frequency of the PPARGC1A Gly/Gly + PPARD CC genotype is associated with elite-level endurance athletes.
Mitochondrial biogenesis related endurance genotype score and sports performance in athletes
Publisher: Elsevier BV
Date: 2011
DOI: 10.1016/J.MITO.2010.07.004
Abstract: We determined the probability of in iduals having the 'optimal' mitochondrial biogenesis related endurance polygenic profile, and compared the endurance polygenic profile of Israeli (Caucasian) endurance athletes (n = 74), power athletes (n = 81), and non-athletes (n = 240). We computed a mitochondrial biogenesis related 'endurance genotype score' (EGS, scoring from 0 to 100) from the accumulated combination of six polymorphisms in the PPARGC1A-NRF-TFAM pathway. Some of the variant alleles of the polymorphisms studied were so infrequent, that the probability of possessing an 'optimal' EGS (= 100) was 0% in the entire study population. However, the EGS was significantly higher (P<0.001) in endurance athletes (38.9 ± 17.1) compared with controls (30.6 ± 12.4) or power athletes (29.0 ± 11.2). In summary, although the probability of an in idual possessing a theoretically 'optimal' genetic background for endurance sports is very low, in general endurance athletes have a polygenic profile that is more suitable for mitochondrial biogenesis.
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National Health And Medical Research Council
Location: No location found
Zinman College Of Physical Education And Sport Sciences
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