HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Doi, Y. Articles by Kiyohara, Y. Search for Related Content PubMed PubMed Citation Articles by Doi, Y. Articles by Kiyohara, Y. Social Bookmarking                What's this?

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

The Hisayama Study

¹ Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
² Department of Environmental Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
³ Laboratory for Genotyping, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Yokohama, Japan

Address correspondence and reprint requests to Yasufumi Doi, MD, Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan. E-mail: doi{at}intmed2.med.kyushu-u.ac.jp

Abbreviations: IFG, impaired fasting glycemia; IGT, impaired glucose tolerance; K_ATP channel, ATP-sensitive K⁺ channel; NGT, normal glucose tolerance; OGTT, oral glucose tolerance test; PAR, population-attributable risk

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.

RESEARCH DESIGN AND 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.

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?