Journal
DIABETOLOGIA
Volume 52, Issue 5, Pages 834-843Publisher
SPRINGER
DOI: 10.1007/s00125-009-1290-2
Keywords
Association study; Chinese; GCK; GCKR; Obesity; Type 2 diabetes
Categories
Funding
- National Natural Science Foundation of China [30571562]
- Chinese Academy of Sciences [KSCX2-YW-R-73]
- National Basic Research Program of China [2006CB503902]
- Major Projects of Knowledge Innovation Program [KSCX2-YW-R-116, KSCX1-YW-02]
- Shanghai-Unilever Research Development Fund [CH-2006-0941]
- Medical Research Council [MC_U106188470] Funding Source: researchfish
- MRC [MC_U106188470] Funding Source: UKRI
Ask authors/readers for more resources
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. 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. 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. 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
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available