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

Author

Listed:
  • 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
  • the HALCyon study team

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.

Suggested Citation

  • 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 & th, 2013. "Associations between a Polymorphism in the Pleiotropic GCKR and Age-Related Phenotypes: The HALCyon Programme," PLOS ONE, Public Library of Science, vol. 8(7), pages 1-9, July.
    • Handle: RePEc:plo:pone00:0070045
    DOI: 10.1371/journal.pone.0070045
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