Association of CDKAL1, IGF2BP2, CDKN2A/B, HHEX, SLC30A8, and KCNJ11 With Susceptibility to Type 2 Diabetes in a Japanese Population

  1. Shintaro Omori12,
  2. Yasushi Tanaka2,
  3. Atsushi Takahashi3,
  4. Hiroshi Hirose4,
  5. Atsunori Kashiwagi5,
  6. Kohei Kaku6,
  7. Ryuzo Kawamori7,
  8. Yusuke Nakamura8 and
  9. Shiro Maeda1
  1. 1Laboratory for Diabetic Nephropathy, SNP Research Center, RIKEN, Yokohama, Kanagawa, Japan
  2. 2Department of Internal Medicine, Division of Metabolism and Endocrinology, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan
  3. 3Laboratory for Statistical Analysis, SNP Research Center, RIKEN, Tokyo, Japan
  4. 4Health Center, Keio University School of Medicine, Tokyo, Japan
  5. 5Department of Medicine, Shiga University of Medical Science, Otsu, Shiga, Japan
  6. 6Division of Endocrinology and Metabolism, Department of Internal Medicine, Kawasaki Medical School, Kurashiki, Okayama, Japan
  7. 7Department of Medicine, Metabolism and Endocrinology, School of Medicine, Juntendo University, Tokyo, Japan
  8. 8Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan
  1. Address correspondence and reprint requests to Shiro Maeda, Laboratory for Diabetic Nephropathy, SNP Research Center, RIKEN, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan. E-mail: smaeda{at}src.riken.jp

Abstract

OBJECTIVE—Recently, several genes have been shown to be associated with an increased risk of type 2 diabetes by genome-wide association studies in white populations. To further investigate the involvement of these polymorphisms in conferring susceptibility to type 2 diabetes, we examined the association of 14 single nucleotide polymorphisms (SNPs) within 11 candidate loci with type 2 diabetes in a Japanese population.

RESEARCH DESIGN AND METHODS—We analyzed 14 SNPs (rs4402960 in IGF2BP2, rs10811661 in CDKN2A/B, rs1111875 and rs7923837 in HHEX, rs13266634 in SLC30A8, rs1113132 and rs11037909 in EXT2, rs9939609 and rs8050136 in FTO, rs7756992 in CDKAL1, rs1801282 in PPARG Pro12Ara, rs5219 in KCNJ11 Glu23Lys, rs7480010 in LOC387761, and rs9300039 in Ch11) in 1,630 Japanese subjects with type 2 diabetes and in 1,064 control subjects by using an invader assay or a TaqMan assay.

RESULTS—Among the 11 loci examined, 6 were significantly associated with type 2 diabetes in our population by a logistic regression analysis, similar to previously reported results (rs4402960, P = 0.00009; rs10811661, P = 0.0024; rs5219, P = 0.0034; rs1111875, P = 0.0064; rs13266634, P = 0.0073; rs7756992, P = 0.0363). In this population, the remaining five loci were not significantly associated with type 2 diabetes. In addition, we identified significant association of the SNPs in FTO gene with BMI in the control subjects.

CONCLUSIONS—We have identified 6 of the 11 loci that were identified by genome-wide association studies in white populations, and these loci are considered strong candidates for type 2 diabetes susceptibility across different ethnicities.

Footnotes

  • Published ahead of print at http://diabetes.diabetesjournals.org on 27 December 2007. DOI: 10.2337/db07-0979.

    Additional information for this article can be found in an online appendix at http://dx.doi.org/10.2337/db07-0979.

    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 December 12, 2007.
    • Received July 14, 2007.
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  1. Published online before print December 27, 2007, doi: 10.2337/db07-0979 Diabetes March 2008 vol. 57 no. 3 791-795
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