Impact of Kir6.2 E23K Polymorphism on the Development of Type 2 Diabetes in a General Japanese Population: the Hisayama Study

Abstract

Objective: The association between the E23K polymorphism of K_ATP channel subunit Kir6.2 and diabetes has been reported in Caucasians, but not in Asians. We examined this issue in follow-up and cross-sectional studies in a general Japanese population.

Methods: In a 14-year follow-up study of 976 subjects aged 40 to 79 years with normal glucose tolerance (NGT), we investigated the impact of E23K polymorphism on change of glucose tolerance status using a 75-g oral glucose tolerance test. Additionally, we confirmed this association in a cross-sectional survey of 2,862 subjects.

Results: In the follow-up study, the frequencies of the K/K genotype or K allele were significantly higher in subjects with conversion from NGT to diabetes than in those in whom NGT was maintained (genotypes: p=0.01; alleles: p=0.008). In multivariate analysis, the risk for progression to diabetes was significantly higher in subjects with the E/K (odds ratio (OR)=2.10, 95% CI=1.16-3.83) and K/K genotypes (OR=2.40, 95% CI=1.01-5.70, p for trend=0.01) compared to those with the E/E genotype after adjustment for confounding factors, namely, age, sex, fasting plasma glucose, family history of diabetes, BMI, physical activity, current drinking and current smoking. In the cross-sectional study, the frequencies of the K/K genotype or K allele were also significantly higher in diabetes than in NGT p=0.006 for genotypes, p=0.001 for alleles).

Conclusions: Our findings suggest that the Kir6.2 E23K polymorphism is an independent genetic risk factor for diabetes in the general Japanese population.