ORCID Profile
0000-0003-2789-2216
Current Organisations
University Hospitals Bristol NHS Foundation Trust
,
University of Exeter
,
University of Bristol
,
University of Bath
,
Sports Cardiology UK
,
Royal College of Physicians
,
Journal of Congenital Cardiology
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Publisher: Oxford University Press (OUP)
Date: 07-01-2013
DOI: 10.1093/HMG/DDS552
Publisher: BMJ
Date: 09-2008
Publisher: BMJ
Date: 11-10-2010
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2013
DOI: 10.1161/CIRCGENETICS.113.000191
Abstract: Association between the C677T polymorphism of the methylene tetrahydrofolate reductase ( MTHFR ) gene and congenital heart disease (CHD) is contentious. We compared genotypes between CHD cases and controls and between mothers of CHD cases and controls. We placed our results in context by conducting meta-analyses of previously published studies. Among 5814 cases with primary genotype data and 10 056 controls, there was no evidence of association between MTHFR C677T genotype and CHD risk (odds ratio [OR], 0.96 [95% confidence interval, 0.87–1.07]). A random-effects meta-analysis of all studies (involving 7697 cases and 13 125 controls) suggested the presence of association (OR, 1.25 [95% confidence interval, 1.03–1.51] P =0.022) but with substantial heterogeneity among contributing studies (I 2 =64.4%) and evidence of publication bias. Meta-analysis of large studies only (defined by a variance of the log OR .05), which together contributed 83% of all cases, yielded no evidence of association (OR, 0.97 [95% confidence interval, 0.91–1.03]) without significant heterogeneity (I 2 =0). Moreover, meta-analysis of 1781 mothers of CHD cases (829 of whom were genotyped in this study) and 19 861 controls revealed no evidence of association between maternal C677T genotype and risk of CHD in offspring (OR, 1.13 [95% confidence interval, 0.87–1.47]). There was no significant association between MTHFR genotype and CHD risk in large studies from regions with different levels of dietary folate. The MTHFR C677T polymorphism, which directly influences plasma folate levels, is not associated with CHD risk. Publication biases appear to substantially contaminate the literature with regard to this genetic association.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2012
DOI: 10.1161/CIRCGENETICS.111.962035
Abstract: Tetralogy of Fallot (TOF) is the commonest cyanotic form of congenital heart disease. In 80% of cases, TOF behaves as a complex genetic condition exhibiting significant heritability. As yet, no common genetic variants influencing TOF risk have been robustly identified. Two hundred and seven haplotype-tagging single nucleotide polymorphisms in 22 candidate genes were genotyped in a test cohort comprising 362 nonsyndromic British white patients with TOF together with 717 unaffected parents of patients and 183 unrelated healthy controls. Single nucleotide polymorphisms with suggestive evidence of association in the test cohort ( P .01) were taken forward for genotyping in an independent replication cohort comprising 392 cases of TOF, 218 unaffected parents of patients, and 1319 controls. Significant association was observed for 1 single nucleotide polymorphism, rs11066320 in the PTPN11 gene, in both the test and the replication cohort. Genotype at rs11066320 was associated with a per-allele odds ratio of 1.34 (95% confidence interval [CI], 1.19 to 1.52 P =2.9×10 −6 ) in the total cohort of TOF cases and controls this remained highly significant after Bonferroni correction for 207 analyses (corrected P =0.00061). Genotype at rs11066320 was responsible for a population-attributable risk of TOF of approximately 10%. Common variation in the linkage disequilibrium block including the PTPN11 gene contributes to the risk of nonsyndromic TOF. Rare mutations in PTPN11 are known to cause the autosomal dominant condition Noonan syndrome, which includes congenital heart disease, by upregulating Ras/mitogen-activated protein kinase (MAPK) signaling. Our results suggest a role for milder perturbations in PTPN11 function in sporadic, nonsyndromic congenital heart disease.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 20-12-2022
Abstract: Peak oxygen consumption (peak V ̇ O 2 $$ \\dot{\\mathrm{V}}{\\mathrm{O}}_2 $$ ) is traditionally ided (“ratio‐scaled”) by body mass (BM) for clinical interpretation. Yet, it is unknown whether ratio‐scaling to BM can produce a valid size‐independent expression of peak V ̇ O 2 $$ \\dot{\\mathrm{V}}{\\mathrm{O}}_2 $$ in people with a Fontan circulation. Furthermore, people with a Fontan circulation have deficits in lean mass, and it is unexplored whether using different measures of body composition may improve scaling validity. The objective was to assess the validity of different scaling denominators (BM, stature, body surface area, fat‐free mass, lean mass, and appendicular lean mass using ratio and allometric scaling). Eighty‐nine participants (age: 23.3±6.7 years 53% female) with a Fontan circulation had their cardiorespiratory fitness and body composition measured by cardiopulmonary exercise testing and dual‐energy x‐ray absorptiometry. Ratio and allometric (log‐linear regression) scaling was performed and Pearson correlations assessed scaling validity. Scaling denominators BM ( r =−0.25, P =0.02), stature ( r =0.46, P .001), and body surface area (0.23, P =0.03) were significantly correlated with their respective ratio‐scaled expressions of peak V ̇ O 2 $$ \\dot{\\mathrm{V}}{\\mathrm{O}}_2 $$ , but fat‐free mass, lean mass, or appendicular lean mass were not ( r ≤0.11 R 2 =1%). Allometrically expressed peak V ̇ O 2 $$ \\dot{\\mathrm{V}}{\\mathrm{O}}_2 $$ resulted in no significant correlation with any scaling denominator ( r =≤0.23 R 2 =≤4%). The traditional and accepted method of ratio‐scaling to BM is invalid because it fails to create a size‐independent expression of peak V ̇ O 2 $$ \\dot{\\mathrm{V}}{\\mathrm{O}}_2 $$ in people with a Fontan circulation. However, ratio‐scaling to measures of body composition (fat‐free mass, lean mass, and appendicular lean mass) and allometric techniques can produce size‐independent expressions of peak V ̇ O 2 $$ \\dot{\\mathrm{V}}{\\mathrm{O}}_2 $$ in people with a Fontan circulation.
Publisher: Public Library of Science (PLoS)
Date: 24-03-2009
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
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
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 Alan Graham Stuart.