Impact of Kir6.2 E23K polymorphism on the development of type 2 diabetes in a general Japanese population

The hisayama study

Yasufumi Doi, Michiaki Kubo, Toshiharu Ninomiya, Koji Yonemoto, Masanori Iwase, Hisatomi Arima, Jun Hata, Yumihiro Tanizaki, Mitsuo Iida, Yutaka Kiyohara

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)2829-2833
Number of pages5
JournalDiabetes
Volume56
Issue number11
DOIs
Publication statusPublished - 01-11-2007
Externally publishedYes

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Type 2 Diabetes Mellitus
Genotype
Glucose
Alleles
Population
Cross-Sectional Studies
Age Factors
Glucose Tolerance Test
Drinking
Fasting
Research Design
Multivariate Analysis
Adenosine Triphosphate
Smoking
Odds Ratio
Exercise

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Doi, Yasufumi ; Kubo, Michiaki ; Ninomiya, Toshiharu ; Yonemoto, Koji ; Iwase, Masanori ; Arima, Hisatomi ; Hata, Jun ; Tanizaki, Yumihiro ; Iida, Mitsuo ; Kiyohara, Yutaka. / Impact of Kir6.2 E23K polymorphism on the development of type 2 diabetes in a general Japanese population : The hisayama study. In: Diabetes. 2007 ; Vol. 56, No. 11. pp. 2829-2833.
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title = "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 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.",
author = "Yasufumi Doi and Michiaki Kubo and Toshiharu Ninomiya and Koji Yonemoto and Masanori Iwase and Hisatomi Arima and Jun Hata and Yumihiro Tanizaki and Mitsuo Iida and Yutaka Kiyohara",
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Doi, Y, Kubo, M, Ninomiya, T, Yonemoto, K, Iwase, M, Arima, H, Hata, J, Tanizaki, Y, Iida, M & Kiyohara, Y 2007, 'Impact of Kir6.2 E23K polymorphism on the development of type 2 diabetes in a general Japanese population: The hisayama study', Diabetes, vol. 56, no. 11, pp. 2829-2833. https://doi.org/10.2337/db06-1709

Impact of Kir6.2 E23K polymorphism on the development of type 2 diabetes in a general Japanese population : The hisayama study. / Doi, Yasufumi; Kubo, Michiaki; Ninomiya, Toshiharu; Yonemoto, Koji; Iwase, Masanori; Arima, Hisatomi; Hata, Jun; Tanizaki, Yumihiro; Iida, Mitsuo; Kiyohara, Yutaka.

In: Diabetes, Vol. 56, No. 11, 01.11.2007, p. 2829-2833.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Impact of Kir6.2 E23K polymorphism on the development of type 2 diabetes in a general Japanese population

T2 - The hisayama study

AU - Doi, Yasufumi

AU - Kubo, Michiaki

AU - Ninomiya, Toshiharu

AU - Yonemoto, Koji

AU - Iwase, Masanori

AU - Arima, Hisatomi

AU - Hata, Jun

AU - Tanizaki, Yumihiro

AU - Iida, Mitsuo

AU - Kiyohara, Yutaka

PY - 2007/11/1

Y1 - 2007/11/1

N2 - 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.

AB - 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.

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