title: Association of GCKR rs780094, alone or in combination with GCK rs1799884, with type 2 diabetes and related traits in a Han Chinese population.
abstract: OBJECTIVE
  The GCKR rs780094 and GCK rs1799884 polymorphisms have been reported to be associated with dyslipidaemia and type 2 diabetes in white Europeans. The aim of this study was to replicate these associations in Han Chinese individuals and to identify the potential mechanisms underlying these associations.
  
  
  METHODS
  The single nucleotide polymorphisms rs780094 and rs1799884 were genotyped in a population-based sample of Han Chinese individuals (n = 3,210) and tested for association with risk of type 2 diabetes and related phenotypes.
  
  
  RESULTS
  The GCKR rs780094 A allele was marginally associated with reduced risk of type 2 diabetes (OR 0.85, 95% CI 0.73-1.00, p value under an additive model [p((add))] = 0.05) and significantly associated with reduced risk of impaired fasting glucose (IFG) or type 2 diabetes (OR 0.86, 95% CI 0.77-0.96, p([add]) = 0.0032). It was also significantly associated with decreased fasting glucose and increased HOMA of beta cell function (HOMA-B) and fasting triacylglycerol levels (p([add]) = 0.0169-5.3 x 10(-6)), but not with HOMA of insulin sensitivity (HOMA-S). The associations with type 2 diabetes and IFG remained significant after adjustment for BMI, while adjustment for HOMA-B abolished the associations. The GCKR rs780094 was also associated with obesity and BMI, independently of its association with type 2 diabetes. The GCK rs1799884 A allele was significantly associated with decreased HOMA-B (p([add]) = 0.0005), but not with type 2 diabetes or IFG. Individuals with increasing numbers of risk alleles for both variants had significantly lower HOMA-B (p([add]) = 5.8 x 10(-5)) in the combined analysis.
  
  
  CONCLUSIONS
  Consistent with observations in white Europeans, the GCKR rs780094 polymorphism contributes to the risk of type 2 diabetes and dyslipidaemia in Han Chinese individuals. In addition, we showed that the effect on type 2 diabetes is probably mediated through impaired beta cell function rather than through obesity.
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, People's Republic of China.
authors.forename: Q
authors.initials: Q
authors.lastname: Qi
authors.forename: Y
authors.initials: Y
authors.lastname: Wu
authors.forename: H
authors.initials: H
authors.lastname: Li
authors.forename: R J F
authors.initials: RJ
authors.lastname: Loos
authors.forename: F B
authors.initials: FB
authors.lastname: Hu
authors.forename: L
authors.initials: L
authors.lastname: Sun
authors.forename: L
authors.initials: L
authors.lastname: Lu
authors.forename: A
authors.initials: A
authors.lastname: Pan
authors.forename: C
authors.initials: C
authors.lastname: Liu
authors.forename: H
authors.initials: H
authors.lastname: Wu
authors.forename: L
authors.initials: L
authors.lastname: Chen
authors.forename: Z
authors.initials: Z
authors.lastname: Yu
authors.forename: X
authors.initials: X
authors.lastname: Lin
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000368:Aged; D044466:Asian People / Q000235:genetics*; D049628:Body Size; D002097:C-Reactive Protein / Q000378:metabolism; D002681:China; D004247:DNA / Q000097:blood / Q000235:genetics / Q000302:isolation & purification; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D000081410:Germinal Center Kinases; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000453:epidemiology; D050177:Overweight / Q000453:epidemiology; D011110:Polymorphism, Genetic; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012307:Risk Factors; D044465:White People / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C485100:GCKR protein, human; D000081410:Germinal Center Kinases; D007328:Insulin; D002097:C-Reactive Protein; D004247:DNA; D017346:Protein Serine-Threonine Kinases