Variations in KCNQ1 Are Associated with Type 2 Diabetes and Beta Cell Function in a Chinese Population

Aims/hypothesis: Recent genome-wide association studies in East Asian populations reported that single nucleotide polymorphisms (SNPs) in KCNQ1 are associated with type 2 diabetes. The aim of this study was to validate this finding in a Chinese population.

Methods: We genotyped four SNPs, rs2074196, rs2237892, rs2237895 and rs2237897, in a group of 3,503 Shanghai Chinese individuals, comprising 1,769 type 2 diabetic patients and 1,734 normoglycaemic controls. Both the cases and the controls were extensively phenotyped for anthropometric and biochemical traits related to glucose metabolism. Arginine stimulation tests under fasting conditions were performed in a subgroup of 466 cases.

Results: All four of the SNPs were associated with type 2 diabetes, with rs2237892 showing strongest evidence for association (OR 1.532, 95% CI 1.381-1.698, p = 5.0 x 10(-16)). The SNP rs2237897 was associated with both acute insulin and C-peptide response after arginine stimulation in a subgroup of cases (p = 0.0471 and p = 0.0156, respectively). The SNP rs2237895 was associated with both first- and second-phase insulin secretion in the controls (p = 0.0334 and p = 0.0002, respectively).

Conclusions/interpretation: In this study we found that KCNQ1 was associated with type 2 diabetes susceptibility in a Chinese population, possibly through its effect on beta cell function.