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

<h4>Background</h4>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...

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Main Authors: 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, HALCyon study team
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0070045
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author 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
HALCyon study team
author_facet 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
HALCyon study team
author_sort Tamuno Alfred
collection DOAJ
description <h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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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spelling doaj-art-25a421163d1f41b489d0838e87b9e1b72025-08-20T02:35:44ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0187e7004510.1371/journal.pone.0070045Associations between a polymorphism in the pleiotropic GCKR and Age-related phenotypes: the HALCyon programme.Tamuno AlfredYoav Ben-ShlomoRachel CooperRebecca HardyIan J DearyJane ElliottSarah E HarrisMika KivimakiMeena KumariChris PowerJohn M StarrDiana KuhIan N M DayHALCyon study team<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.https://doi.org/10.1371/journal.pone.0070045
spellingShingle 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
HALCyon study team
Associations between a polymorphism in the pleiotropic GCKR and Age-related phenotypes: the HALCyon programme.
PLoS ONE
title Associations between a polymorphism in the pleiotropic GCKR and Age-related phenotypes: the HALCyon programme.
title_full Associations between a polymorphism in the pleiotropic GCKR and Age-related phenotypes: the HALCyon programme.
title_fullStr Associations between a polymorphism in the pleiotropic GCKR and Age-related phenotypes: the HALCyon programme.
title_full_unstemmed Associations between a polymorphism in the pleiotropic GCKR and Age-related phenotypes: the HALCyon programme.
title_short Associations between a polymorphism in the pleiotropic GCKR and Age-related phenotypes: the HALCyon programme.
title_sort associations between a polymorphism in the pleiotropic gckr and age related phenotypes the halcyon programme
url https://doi.org/10.1371/journal.pone.0070045
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