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PLoS One. 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.

Author information

1
School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom. tamuno.alfred@bristol.ac.uk

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.

PMID:
23894584
PMCID:
PMC3720952
DOI:
10.1371/journal.pone.0070045
[Indexed for MEDLINE]
Free PMC Article
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