Abstract
AIMS/HYPOTHESIS: Two recent genome-wide association studies have identified several novel type 2 diabetes susceptibility variants in intron 15 of the KCNQ1 gene. We aimed to evaluate the effects of the variants in KCNQ1 on type 2 diabetes and metabolic traits in the population of mainland China. METHODS: Three candidate single nucleotide polymorphisms were genotyped in 1,912 individuals with type 2 diabetes and 2,041 normal controls using the ligase detection reaction method. RESULTS: We confirmed the association of KCNQ1 with type 2 diabetes in the population of mainland China. Allele frequency ORs of the three single nucleotide polymorphisms (SNPs) were: rs2237892 (OR 1.19, 95% CI 1.08-1.31, p = 3.0 x 10(-4)); rs2237895 (OR 1.20, 95% CI 1.09-1.32, p = 1.9 x 10(-4)); and rs2237897 (OR 1.24, 95% CI 1.13-1.36, p = 3.9 x 10(-5)). We also found a significant difference in the distribution of the global haplotypes between the type 2 diabetes group and the normal control group (p = 2.6 x 10(-5)). In addition, in the control group SNP rs2237892 was marginally associated with increasing fasting plasma glucose and SNPs rs2237892 and rs2237897 were associated with HbA(1c). Furthermore, for all three variants, homozygous carriers of the diabetes-associated allele had significantly decreased BMI and waist circumferences. CONCLUSIONS/INTERPRETATION: Our investigation confirmed the effects of KCNQ1 variants on type 2 diabetes risk in the Chinese population.