ORCID Profile
0000-0002-8485-8930
Current Organisation
University of Reading
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Publisher: Oxford University Press (OUP)
Date: 12-2015
DOI: 10.1530/EJE-15-0839
Abstract: Given the role of uncoupling protein 2 (UCP2) in the accumulation of fat in the hepatocytes and in the enhancement of protective mechanisms in acute ethanol intake, we hypothesised that UCP2 polymorphisms are likely to cause liver disease through their interactions with obesity and alcohol intake. To test this hypothesis, we investigated the interaction between tagging polymorphisms in the UCP2 gene (rs2306819, rs599277 and rs659366), alcohol intake and obesity traits such as BMI and waist circumference (WC) on alanine aminotransferase (ALT) and gamma glutamyl transferase (GGT) in a large meta-analysis of data sets from three populations ( n =20 242). The study populations included the Northern Finland Birth Cohort 1966 ( n =4996), Netherlands Study of Depression and Anxiety ( n =1883) and LifeLines Cohort Study ( n =13 363). Interactions between the polymorphisms and obesity and alcohol intake on dichotomised ALT and GGT levels were assessed using logistic regression and the likelihood ratio test. In the meta-analysis of the three cohorts, none of the three UCP2 polymorphisms were associated with GGT or ALT levels. There was no evidence for interaction between the polymorphisms and alcohol intake on GGT and ALT levels. In contrast, the association of WC and BMI with GGT levels varied by rs659366 genotype ( P interaction =0.03 and 0.007, respectively adjusted for age, gender, high alcohol intake, diabetes, hypertension and serum lipid concentrations). In conclusion, our findings in 20 242 in iduals suggest that UCP2 gene polymorphisms may cause liver dysfunction through the interaction with body fat rather than alcohol intake.
Publisher: Springer Science and Business Media LLC
Date: 05-02-2013
DOI: 10.1038/IJO.2013.6
Publisher: Springer Science and Business Media LLC
Date: 14-12-2008
DOI: 10.1038/NG.287
Publisher: Springer Science and Business Media LLC
Date: 27-01-2020
DOI: 10.1007/S40200-019-00480-5
Abstract: Adverse effects of maternal vitamin D deficiency have been linked to adverse pregnancy outcomes. We investigated the relationship between maternal vitamin D status and newborn anthropometry measurements using a genetic approach and examined the interaction between genetic variations in involved in vitamin D synthesis and metabolism and maternal vitamin D concentrations on newborn anthropometry. The study was conducted in 183 pregnant Indonesian Minangkabau women. Genetic risk scores (GRSs) were created using six vitamin D–related single nucleotide polymorphisms and their association with 25-hydroxyvitamin D [25(OH)D] levels and newborn anthropometry (183 infants) were investigated. There was no significant association between maternal 25(OH)D concentrations and newborn anthropometry measurements ( P 0.05, for all comparisons). After correction for multiple testing using Bonferroni correction, GRS was significantly associated with 25(OH)D in the third trimester ( P = 0.004). There was no association between GRS and newborn anthropometric measurements however, there was an interaction between GRS and 25(OH)D on head circumference ( P = 0.030), where mothers of neonates with head circumference 35 cm had significantly lower 25(OH)D if they carried ≥4 risk alleles compared to those who carried ≤3 risk alleles. Our findings demonstrate the impact of vitamin D-related GRS on 25(OH)D and provides evidence for the effect of vitamin D-related GRS on newborn anthropometry through the influence of serum 25(OH)D levels among Indonesian pregnant women. Even though our study is a prospective cohort, before the implementation of vitamin D supplementation programs in Indonesia to prevent adverse pregnancy outcomes, further large studies are required to confirm our findings.
Publisher: MDPI AG
Date: 20-10-2022
DOI: 10.3390/NU14204408
Abstract: Twin studies suggest a considerable genetic contribution to the variability in 25-hydroxyvitamin D (25(OH)D) concentrations, reporting heritability estimates up to 80% in some studies. While genome-wide association studies (GWAS) suggest notably lower rates (13–16%), they have identified many independent variants that associate with serum 25(OH)D concentrations. These discoveries have provided some novel insight into the metabolic pathway, and in this review we outline findings from GWAS studies to date with a particular focus on 35 variants which have provided replicating evidence for an association with 25(OH)D across independent large-scale analyses. Some of the 25(OH)D associating variants are linked directly to the vitamin D metabolic pathway, while others may reflect differences in storage capacity, lipid metabolism, and pathways reflecting skin properties. By constructing a genetic score including these 25(OH)D associated variants we show that genetic differences in 25(OH)D concentrations persist across the seasons, and the odds of having low concentrations ( nmol/L) are about halved for in iduals in the highest 20% of vitamin D genetic score compared to the lowest quintile, an impact which may have notable influences on retaining adequate levels. We also discuss recent studies on personalized approaches to vitamin D supplementation and show how Mendelian randomization studies can help inform public health strategies to reduce adverse health impacts of vitamin D deficiency.
Publisher: Springer Science and Business Media LLC
Date: 12-10-2020
DOI: 10.1186/S12263-020-00678-W
Abstract: Cardiometabolic diseases are complex traits which are influenced by several single nucleotide polymorphisms (SNPs). Thus, analysing the combined effects of multiple gene variants might provide a better understanding of disease risk than using a single gene variant approach. Furthermore, studies have found that the effect of SNPs on cardiometabolic traits can be influenced by lifestyle factors, highlighting the importance of analysing gene-lifestyle interactions. In the present study, we investigated the association of 15 gene variants with cardiometabolic traits and examined whether these associations were modified by lifestyle factors such as dietary intake and physical activity. The study included 110 Minangkabau women [aged 25–60 years and body mass index (BMI) 25.13 ± 4.2 kg/m 2 ] from Padang, Indonesia. All participants underwent a physical examination followed by anthropometric, biochemical and dietary assessments and genetic tests. A genetic risk score (GRS) was developed based on 15 cardiometabolic disease-related SNPs. The effect of GRS on cardiometabolic traits was analysed using general linear models. GRS-lifestyle interactions on continuous outcomes were tested by including the interaction term (e.g. lifestyle factor*GRS) in the regression model. Models were adjusted for age, BMI and location (rural or urban), wherever appropriate. There was a significant association between GRS and BMI, where in iduals carrying 6 or more risk alleles had higher BMI compared to those carrying 5 or less risk alleles ( P = 0.018). Furthermore, there were significant interactions of GRS with protein intake on waist circumference (WC) and triglyceride concentrations ( P interaction = 0.002 and 0.003, respectively). Among women who had a lower protein intake (13.51 ± 1.18% of the total daily energy intake), carriers of six or more risk alleles had significantly lower WC and triglyceride concentrations compared with carriers of five or less risk alleles ( P = 0.0118 and 0.002, respectively). Our study confirmed the association of GRS with higher BMI and further showed a significant effect of the GRS on WC and triglyceride levels through the influence of a low-protein diet. These findings suggest that following a lower protein diet, particularly in genetically predisposed in iduals, might be an effective approach for addressing cardiometabolic diseases among Southeast Asian women.
Publisher: Springer Science and Business Media LLC
Date: 2014
Publisher: Springer Science and Business Media LLC
Date: 24-05-2021
DOI: 10.1038/S41366-021-00841-2
Abstract: High milk intake has been associated with cardio-metabolic risk. We conducted a Mendelian Randomization (MR) study to obtain evidence for the causal relationship between milk consumption and cardio-metabolic traits using the lactase persistence ( LCT -13910 C T, rs4988235) variant as an instrumental variable. We tested the association of LCT genotype with milk consumption (for validation) and with cardio-metabolic traits (for a possible causal association) in a meta-analysis of the data from three large-scale population-based studies (1958 British Birth Cohort, Health and Retirement study, and UK Biobank) with up to 417,236 participants and using summary statistics from consortia meta-analyses on intermediate traits ( N = 123,665–697,307) and extended to cover disease endpoints ( N = 86,995–149,821). In the UK Biobank, carriers of ‘T’ allele of LCT variant were more likely to consume milk ( P = 7.02 × 10 −14 ). In meta-analysis including UK Biobank, the 1958BC, the HRS, and consortia-based studies, under an additive model, ‘T’ allele was associated with higher body mass index (BMI) ( P meta-analysis = 4.68 × 10 −12 ) and lower total cholesterol (TC) ( P = 2.40 × 10 −36 ), low-density lipoprotein cholesterol (LDL-C) ( P = 2.08 × 10 −26 ) and high-density lipoprotein cholesterol (HDL-C) ( P = 9.40 × 10 −13 ). In consortia meta-analyses, ‘T’ allele was associated with a lower risk of coronary artery disease (OR:0.86, 95% CI:0.75–0.99) but not with type 2 diabetes (OR:1.06, 95% CI:0.97–1.16). Furthermore, the two-s le MR analysis showed a causal association between genetically instrumented milk intake and higher BMI ( P = 3.60 × 10 −5 ) and body fat (total body fat, leg fat, arm fat and trunk fat P 1.37 × 10 −6 ) and lower LDL-C ( P = 3.60 × 10 −6 ), TC ( P = 1.90 × 10 −6 ) and HDL-C ( P = 3.00 × 10 −5 ). Our large-scale MR study provides genetic evidence for the association of milk consumption with higher BMI but lower serum cholesterol levels. These data suggest no need to limit milk intakes with respect to cardiovascular disease risk, with the suggested benefits requiring confirmation in further studies.
Publisher: Wiley
Date: 12-06-2012
DOI: 10.1111/J.1398-9995.2012.02856.X
Abstract: The hormonal form of vitamin D affects both adaptive and innate immune functions involved in the development of allergies. Certain genotypes have been seen to alter the association between vitamin D deficiency (VDD) and the risk of food sensitization in children. We examined 27 functional single nucleotide polymorphisms (SNPs) in/near selected candidate genes for association with total immunoglobulin E (IgE) and effect modification by 25-hydroxyvitamin D in the 1958 British birth cohort (aged 45 years, n = 4921). A cut-off value of 50 nmol/L was used to define VDD. Four SNPs (in FCER1A, IL13, and CYP24A1) and three SNPs (in IL4 and CYP24A1) were associated with total IgE and specific IgE, respectively, after correction for multiple testing. As in a previous study, MS4A2 (rs512555, P(interaction) = 0.04) and IL4 (rs2243250, P(interaction) = 0.02), and their composite score (P(interaction) = 0.009) modified the association between VDD and allergy-related outcome. Vitamin D deficiency was associated with higher total IgE only in the carriers of the 'C' allele (IL4), which is present in 86% of white Europeans, while only 26% of Chinese and <20% of some African populations are carriers. Our study on white European adults was consistent with a previous study on children from largely non-white ethnic groups, suggesting that IL4 and MS4A2 genotypes modify the association between VDD and allergy risk. The risk allele in IL4 is present in nearly 90% of white Europeans, while less than a quarter are carriers in some other populations, highlighting the need to consider possible ethnic differences in allergy-related responsiveness to VDD.
Publisher: Elsevier BV
Date: 05-2013
DOI: 10.1016/J.ATHEROSCLEROSIS.2013.02.006
Abstract: Circulating levels of 25-hydroxyvitamin D (25OHD) are positively associated with high density lipoprotein (HDL) cholesterol. We sought to replicate a previously reported interaction between APOA5 genotype and vitamin D, and to examine whether HDL-associated genetic loci modify the association between serum 25OHD and HDL cholesterol. We examined whether 42 single nucleotide polymorphisms (SNPs) modify the association between serum 25OHD and HDL cholesterol in the 1958 British Birth cohort (aged 45 years, n = 4978). We identified a borderline interaction between the SNP rs12272004 (near the APOA5) and serum 25OHD on HDL cholesterol (P(interaction) = 0.05). The interaction was particularly prominent among the s les collected during winter (P(interaction) = 0.001). None of the other loci showed an interaction with serum 25OHD concentrations on HDL cholesterol. Our study in 4978 British Whites provides further support that APOA5 genotype modifies the association between vitamin D metabolites and HDL cholesterol.
Publisher: MDPI AG
Date: 23-01-2021
DOI: 10.3390/NU13020326
Abstract: Metabolic diseases have been shown to be associated with low vitamin D status however, the findings have been inconsistent. Hence, the objective of our study was to investigate the relationship between vitamin D status and metabolic disease-related traits in healthy Southeast Asian women and examine whether this relationship was modified by dietary factors using a nutrigenetic study. The study included 110 Minangkabau women (age: 25–60 years) from Padang, Indonesia. Genetic risk scores (GRS) were constructed based on five vitamin D-related single nucleotide polymorphisms (SNPs) (vitamin D-GRS) and ten metabolic disease-associated SNPs (metabolic-GRS). The metabolic-GRS was significantly associated with lower 25-hydroxyvitamin D (25(OH)D) concentrations (p = 0.009) and higher body mass index (BMI) (p = 0.016). Even though the vitamin D-GRS had no effect on metabolic traits (p 0.12), an interaction was observed between the vitamin D-GRS and carbohydrate intake (g) on body fat percentage (BFP) (pinteraction = 0.049), where those in iduals who consumed a high carbohydrate diet (mean ± SD: 319 g/d ± 46) and carried vitamin D-lowering risk alleles had significantly higher BFP (p = 0.016). In summary, we have replicated the association of metabolic-GRS with higher BMI and lower 25(OH)D concentrations and identified a novel interaction between vitamin D-GRS and carbohydrate intake on body fat composition.
Publisher: Public Library of Science (PLoS)
Date: 21-05-2012
Publisher: Springer Science and Business Media LLC
Date: 25-07-2019
Publisher: Elsevier BV
Date: 11-2014
DOI: 10.1016/J.DIABET.2014.01.003
Abstract: 25-hydroxyvitamin D (25OHD) concentrations have been shown to be associated with major clinical outcomes, with a suggestion that in idual risk may vary according to common genetic differences in the vitamin D receptor (VDR) gene. Hence, we tested for the interactions between two previously studied VDR polymorphisms and 25OHD on metabolic and cardiovascular disease-related outcomes in a large population-based study. Interactions between two previously studied VDR polymorphisms (rs7968585 and rs2239179) and 25OHD concentrations on metabolic and cardiovascular disease-related outcomes such as obesity- (body mass index, waist circumference, waist-hip ratio (WHR)), cardiovascular- (systolic and diastolic blood pressure), lipid- (high- and low-density lipoprotein, triglycerides, total cholesterol), inflammatory- (C-reactive protein, fibrinogen, insulin growth factor-1, tissue plasminogen activator) and diabetes- (glycated haemoglobin) related markers were examined in the 1958 British Birth cohort (n up to 5160). Interactions between each SNP and 25OHD concentrations were assessed using linear regression and the likelihood ratio test. After Bonferroni correction, none of the interactions reached statistical significance except for the interaction between the VDR SNP rs2239179 and 25OHD concentrations on waist-hip ratio (WHR) (P=0.03). For every 1nmol/L higher 25OHD concentrations, the association with WHR was stronger among those with two major alleles (-4.0%, P=6.26e(-24)) compared to those with either one or no major alleles (-2.3%, P≤8.201e(-07), for both) of the VDR SNP rs2239179. We found no evidence for VDR polymorphisms acting as major modifiers of the association between 25OHD concentrations and cardio-metabolic risk. Interaction between VDR SNP rs2239179 and 25OHD on WHR warrants further confirmation.
Publisher: Hindawi Limited
Date: 14-10-2019
DOI: 10.1002/DA.22963
Abstract: This study aimed to explore the association between depression and body mass index (BMI), and to investigate whether genetic susceptibility to high BMI is different among in iduals with or without depression. We used data on 251,125 in iduals of white British ancestry from the UK Biobank. We conducted Mendelian randomization (MR) analysis to test for a causal association between depression and BMI using a major depressive disorder (MDD)-related genetic risk score (GRS We found observational and genetic evidence for an association between depression and BMI (MR beta: 0.09, 95% confidence interval [CI] 0.04-0.13). Further, the contribution of genetic risk to high BMI was higher among in iduals with depression compared to controls. Carrying 10 additional BMI increasing alleles was associated with 0.24 standard deviation (SD 95%CI 0.23-0.25) higher BMI among depressed in iduals compared to 0.20 SD (95%CI 0.19-0.21) higher in controls, which corresponds to 3.4 kg and 2.8 kg extra weight for an in idual of average height. Amongst the in idual loci, the evidence for interaction was most notable for a variant near MC4R, a gene known to affect both appetite regulation and the hypothalamic-pituitary adrenal axis (p Genetic predisposition to high BMI was higher among depressed than to nondepressed in iduals. This study provides support for a possible role of MC4R in the link between depression and obesity.
Publisher: BMJ
Date: 31-10-2017
DOI: 10.1136/BMJ.J4761
Publisher: Elsevier BV
Date: 09-2014
Publisher: Springer Science and Business Media LLC
Date: 08-04-2012
DOI: 10.1038/NG.2247
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Vimal Karani.