Association of GCKR rs780094, alone or in combination with GCK rs1799884, with type 2 diabetes and related traits in a Han Chinese population.

Abstract

AIMS/HYPOTHESIS:

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/INTERPRETATION:

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: Q Qi, Y Wu, H Li, R J F Loos, F B Hu, L Sun, L Lu, A Pan, C Liu, H Wu, L Chen, Z Yu, X Lin
• Journal: Diabetologia (Diabetologia) Vol. 52 Issue 5 Pg. 834-43 (May 2009) ISSN: 1432-0428 [Electronic] Germany
• PMID: 19241058 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adaptor Proteins, Signal Transducing
• GCKR protein, human
• Germinal Center Kinases
• Insulin
• C-Reactive Protein
• DNA
• Protein Serine-Threonine Kinases

Topics

• Adaptor Proteins, Signal Transducing (genetics)
• Aged
• Asian People (genetics)
• Body Size
• C-Reactive Protein (metabolism)
• China
• DNA (blood, genetics, isolation & purification)
• Diabetes Mellitus, Type 2 (epidemiology, genetics)
• Female
• Genetic Variation
• Genotype
• Germinal Center Kinases
• Humans
• Insulin (blood)
• Male
• Middle Aged
• Obesity (epidemiology)
• Overweight (epidemiology)
• Polymorphism, Genetic
• Protein Serine-Threonine Kinases (genetics)
• Risk Factors
• White People (genetics)