Associations between a Polymorphism in the Pleiotropic GCKR and Age-Related Phenotypes: The HALCyon Programme
Year: 2013
Type: article
Abstract: BACKGROUND: The glucokinase regulatory protein encoded by GCKR plays an important role in glucose metabolism and a single nucleotide polymorphism (SNP) rs1260326 (P446L) in the gene has been associated with several age-related biomarkers, including triglycerides, glucose, insulin and apolipoproteins. However, associations between SNPs in the gene and other ageing phenotypes such as cognitive and physical capability have not been reported. METHODS: As part of the Healthy Ageing across the Life Course (HALCyon) collaborative research programme, men and women from five UK cohorts aged between 44 and 90+ years were genotyped for rs1260326. Meta-analysis was used to pool within-study genotypic associations between the SNP and several age-related phenotypes, including body mass index (BMI), blood lipid levels, lung function, and cognitive and physical capability. RESULTS: We confirm the associations between the minor allele of the SNP and higher triglycerides and lower glucose levels. We also observed a triglyceride-independent association between the minor allele and lower BMI (pooled beta on z-score= -0.04, p-value=0.0001, n=16,251). Furthermore, there was some evidence for gene-environment interactions, including physical activity attenuating the effects on triglycerides. However, no associations were observed with measures of cognitive and physical capability. CONCLUSION: Findings from middle-aged to older adults confirm associations between rs1260326 GCKR and triglycerides and glucose, suggest possible gene-environment interactions, but do not provide evidence that its relevance extends to cognitive and physical capability.
Source: PLoS ONE
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,382
Funders: John D. and Catherine T. MacArthur Foundation, University of Portsmouth, Wellcome Trust, National Institute for Health and Care Research, British Heart Foundation, Age UK, University of Southampton, University College London, Newcastle University, University of Edinburgh, University of Glasgow, Cardiff University, Health and Safety Executive, University of Aberdeen, University of Bristol, Academy of Finland, Centre for Cognitive Ageing and Cognitive Epidemiology, National Institutes of Health, Directorate for Biological Sciences, Agency for Healthcare Research and Quality, Medical Research Council, Engineering and Physical Sciences Research Council, Biotechnology and Biological Sciences Research Council, Economic and Social Research Council, National Institute on Aging, National Heart, Lung, and Blood Institute
Awards: G1093300281, G1137313802, G1167024831, G1466358154, G1492072473, G1896713975, G2064885621, HALCyon Healthy Ageing across the Life Course, G2307454678, G2425175678, Health behaviors over the adult lifecourse and cognitive aging, G2507151542, G2594517499, G269567959, G2719016821, G2751663742, Determinants of healthy ageing in the Whitehall II study, G2824707892, G2928833717, G2953204649, G3251713059, G3278553629, G3349769430, G3747358395, G443238052, G4522451727, G4641403149, G4746977625, G4856618060, G4942547004, G4950536974, G5067462658, G5175381056, G5208912463, G538581767, G5412976545, G5502349062, G5503240538, G5568298347, A national DNA control series for genetic case-control studies based on the British 1958 birth cohort, G6060264546, G6122601559, G6172210748, G6239859655, G6354209809, G643113813, G6661414329, G690763772, G695167419, A genome-wide association study of non-pathological cognitive ageing, G7243315025, G7374949320, G7572990571, G7584390538, G7627314639, Vascular risk and functional decline in old age (renewal), G7782480062, Socio-economic status and heterogeneity in aging, G7900679853, Socioeconomic gradient in CHD in early old age, G8648435156, G9000120579, G9000178614
OpenAlex ID: W2106085838