Association Studies of Variants in the Genes Involved in Pancreatic β-Cell Function in Type 2 Diabetes in Japanese Subjects

  1. Norihide Yokoi1,
  2. Masao Kanamori2,
  3. Yukio Horikawa3,
  4. Jun Takeda3,
  5. Tokio Sanke4,
  6. Hiroto Furuta5,
  7. Kishio Nanjo5,
  8. Hiroyuki Mori6,
  9. Masato Kasuga6,
  10. Kazuo Hara7,
  11. Takashi Kadowaki7,
  12. Yukio Tanizawa8,
  13. Yoshitomo Oka9,
  14. Yukiko Iwami10,
  15. Hisako Ohgawara10,
  16. Yuichiro Yamada11,
  17. Yutaka Seino11,
  18. Hideki Yano12,
  19. Nancy J. Cox13 and
  20. Susumu Seino1
  1. 1Division of Cellular and Molecular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
  2. 2Division of Health and Preventive Medicine, Department of Lifelong Sport, Biwako Seikei Sport College, Shiga, Japan
  3. 3Department of Endocrinology, Diabetes and Rheumatology, Division of Bioregulatory Medicine, Gifu University School of Medicine, Gifu, Japan
  4. 4Department of Clinical Laboratory Medicine, Wakayama University of Medical Science, Wakayama, Japan
  5. 5First Department of Medicine, Wakayama University of Medical Science, Wakayama, Japan
  6. 6Department of Clinical Molecular Medicine, Division of Diabetes and Digestive and Kidney Diseases, Kobe University Graduate School of Medicine, Kobe, Japan
  7. 7Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
  8. 8Division of Molecular Analysis of Human Disorders, Department of Bio-Signal Analysis, Yamaguchi University Graduate School of Medicine, Ube, Japan
  9. 9Division of Molecular Metabolism and Diabetes, Tohoku University Graduate School of Medicine, Sendai, Japan
  10. 10Division of Cell Replacement and Regenerative Medicine, Medical Research Institute, School of Medicine, Tokyo Women’s Medical University, Tokyo, Japan
  11. 11Department of Diabetes and Clinical Nutrition, Kyoto University Graduate School of Medicine, Kyoto, Japan
  12. 12Department of Internal Medicine, Hikone Municipal Hospital, Shiga, Japan
  13. 13Departments of Medicine and Human Genetics, University of Chicago, Chicago, Illinois
  1. Address correspondence and reprint requests to Susumu Seino, Division of Cellular and Molecular Medicine, Kobe University Graduate School of Medicine, Chuo-ku, Kobe 650-0017, Japan. E-mail: seino{at}med.kobe-u.ac.jp

Abstract

Because impaired insulin secretion is characteristic of type 2 diabetes in Asians, including Japanese, the genes involved in pancreatic β-cell function are candidate susceptibility genes for type 2 diabetes. We examined the association of variants in genes encoding several transcription factors (TCF1, TCF2, HNF4A, ISL1, IPF1, NEUROG3, PAX6, NKX2–2, NKX6–1, and NEUROD1) and genes encoding the ATP-sensitive K+ channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) with type 2 diabetes in a Japanese cohort of 2,834 subjects. The exon 16 −3c/t variant rs1799854 in ABCC8 showed a significant association (P = 0.0073), and variants in several genes showed nominally significant associations (P < 0.05) with type 2 diabetes. Although the E23K variant rs5219 in KCNJ11 showed no association with diabetes in Japanese (for the K allele, odds ratio [OR] 1.08 [95% CI 0.97–1.21], P = 0.15), 95% CI around the OR overlaps in meta-analysis of European populations, suggesting that our results are not inconsistent with the previous studies. This is the largest association study so far conducted on these genes in Japanese and provides valuable information for comparison with other ethnic groups.

Footnotes

  • Additional information for this article can be found in an online appendix at http://diabetes.diabetesjournals.org.

    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.

    • Accepted May 22, 2006.
    • Received September 13, 2005.
| Table of Contents