Associations between a polymorphism in the pleiotropic GCKR and Age-related phenotypes: the HALCyon programme.

Cooper, Rachel ORCID: https://orcid.org/0000-0003-3370-5720, Alfred, T, Ben-Shlomo, Y, Cooper, R ORCID: https://orcid.org/0000-0003-3370-5720, Hardy, R, Deary, IJ, Elliott, J, Harris, SE, Kivimaki, M, Kumari, M, Power, C, Starr, JM, Kuh, D, Day, IN and team, HALCyon study (2013) Associations between a polymorphism in the pleiotropic GCKR and Age-related phenotypes: the HALCyon programme. PLoS ONE, 8 (7). ISSN 1932-6203

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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 zscore = 20.04, 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.