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

The Hisayama Study

  1. Yasufumi Doi1,
  2. Michiaki Kubo1,3,
  3. Toshiharu Ninomiya2,
  4. Koji Yonemoto2,
  5. Masanori Iwase1,
  6. Hisatomi Arima2,
  7. Jun Hata2,
  8. Yumihiro Tanizaki1,
  9. Mitsuo Iida1 and
  10. Yutaka Kiyohara2
  1. 1Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
  2. 2Department of Environmental Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
  3. 3Laboratory for Genotyping, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Yokohama, Japan
  1. 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

Abstract

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.

Footnotes

  • Published ahead of print at http://diabetes.diabetesjournals.org on 17 August 2007. DOI: 10.2337/db06-1709.

    The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Received December 7, 2006.
    • Accepted August 10, 2007.
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  1. Diabetes vol. 56 no. 11 2829-2833
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