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Meta-Analysis
. 2013 Jul 23;8(7):e70045.
doi: 10.1371/journal.pone.0070045. Print 2013.

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

Tamuno Alfred  1 , 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; HALCyon study team
Affiliations
Meta-Analysis

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

Tamuno Alfred et al. PLoS One. .

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.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

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