Impact of Kir6.2 E23K polymorphism on the development of type 2 diabetes in a general Japanese population: The Hisayama Study.
OBJECTIVE
The association between the E23K polymorphism of ATP-sensitive K(+) 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 40-79 years with normal glucose tolerance (NGT), we investigated the impact of the 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 2.10 [95% CI 1.16-3.83]) and K/K (2.40 [1.01-5.70], P for trend = 0.01) genotypes than in 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 those with diabetes than in those with NGT (genotypes, P = 0.006; alleles, P = 0.001).


CONCLUSIONS
Our findings suggest that the Kir6.2 E23K polymorphism is an independent genetic risk factor for diabetes in the general Japanese population.
Doi
Yasufumi
Y
Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan. doi@intmed2.med.kyushu-u.ac.jp
Kubo
Michiaki
M
Ninomiya
Toshiharu
T
Yonemoto
Koji
K
Iwase
Masanori
M
Arima
Hisatomi
H
Hata
Jun
J
Tanizaki
Yumihiro
Y
Iida
Mitsuo
M
Kiyohara
Yutaka
Y
D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D018149:Glucose Intolerance / Q000235:genetics; D005951:Glucose Tolerance Test; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics*; D012307:Risk Factors; D000099161:Kcnj11 Channel
D024661:Potassium Channels, Inwardly Rectifying; D000099161:Kcnj11 Channel