title: Associations between a polymorphism in the pleiotropic GCKR and Age-related phenotypes: the HALCyon programme.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom. tamuno.alfred@bristol.ac.uk
authors.forename: Tamuno
authors.initials: T
authors.lastname: Alfred
authors.forename: Yoav
authors.initials: Y
authors.lastname: Ben-Shlomo
authors.forename: Rachel
authors.initials: R
authors.lastname: Cooper
authors.forename: Rebecca
authors.initials: R
authors.lastname: Hardy
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Deary
authors.forename: Jane
authors.initials: J
authors.lastname: Elliott
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Harris
authors.forename: Mika
authors.initials: M
authors.lastname: Kivimaki
authors.forename: Meena
authors.initials: M
authors.lastname: Kumari
authors.forename: Chris
authors.initials: C
authors.lastname: Power
authors.forename: John M
authors.initials: JM
authors.lastname: Starr
authors.forename: Diana
authors.initials: D
authors.lastname: Kuh
authors.forename: Ian N M
authors.initials: IN
authors.lastname: Day
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000502:physiology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics / Q000502:physiology*; D000483:Alleles; D015992:Body Mass Index; D003071:Cognition / Q000502:physiology; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006801:Humans; D008055:Lipids / Q000097:blood; D008168:Lung / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009043:Motor Activity / Q000235:genetics / Q000502:physiology; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012737:Sex Factors; D006113:United Kingdom
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C485100:GCKR protein, human; D008055:Lipids
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