Associations between a Polymorphism in the Pleiotropic GCKR and Age-Related Phenotypes: The HALCyon Programme

Tamuno Alfred, Yoav Ben-Shlomo, Rachel Cooper, Rebecca Hardy, Ian J Deary, Jane Elliott, Sarah E Harris, Mika Kivimaki, Meena Kumari, Chris Power, John M Starr, Diana Kuh, Ian N M Day and the HALCyon study Team

PLOS ONE, 2013, vol. 8, issue 7, 1-9

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.

Date: 2013
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pone00:0070045

DOI: 10.1371/journal.pone.0070045

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