Association of CDKAL1, IGF2BP2, CDKN2A/B, HHEX, SLC30A8 and KCNJ11 with susceptibility to type 2 diabetes in a Japanese population

  1. Shintaro Omori, M.D.1,,2,
  2. Yasushi Tanaka, M.D., Ph.D.2,
  3. Atsushi Takahashi, Ph.D.3,
  4. Hiroshi Hirose, M.D., Ph.D.4,
  5. Atsunori Kashiwagi, M.D., Ph.D.5,
  6. Kohei Kaku, M.D., Ph.D.6,
  7. Ryuzo Kawamori, M.D., Ph.D.7,
  8. Yusuke Nakamura, M.D., Ph.D.8 and
  9. Shiro Maeda, M.D., Ph.D. (smaeda{at}src.riken.jp)1
  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

    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 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 loci 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 5 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.

    Conclusion: 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

      • Received July 14, 2007.
      • Accepted December 12, 2007.

    This Article

    1. Published online before print December 27, 2007, doi: 10.2337/db07-0979
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