Genetic Heterogeneity in Association of the SUMO4 M55V Variant With Susceptibility to Type 1 Diabetes

  1. Shinsuke Noso1,
  2. Hiroshi Ikegami1,
  3. Tomomi Fujisawa1,
  4. Yumiko Kawabata1,
  5. Katsuaki Asano1,
  6. Yoshihisa Hiromine1,
  7. Masako Tsurumaru23,
  8. Shigetaka Sugihara4,
  9. Inkyu Lee5,
  10. Eiji Kawasaki3,
  11. Takuya Awata6 and
  12. Toshio Ogihara1
  1. 1Department of Geriatric Medicine, Osaka University Graduate School of Medicine, Osaka, Japan
  2. 2Clinical Research and Trial Center, Nagasaki University Hospital of Medicine and Dentistry, Nagasaki, Japan
  3. 3Department of Metabolism/Diabetes and Clinical Nutrition, Nagasaki University Hospital of Medicine and Dentistry, Nagasaki, Japan
  4. 4Department of Pediatrics, Tokyo Women’s Medical University Daini Hospital, Tokyo, Japan
  5. 5Department of Internal Medicine, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, Korea
  6. 6Division of Endocrinology and Diabetes, Department of Medicine, Saitama Medical School, Saitama, Japan
  1. Address correspondence and reprint requests to Hiroshi Ikegami, MD, Osaka University, Department of Geriatric Medicine, 2-2 Yamadaoka, Suita, Osaka, Japan. E-mail: ikegami{at}


Association studies are a potentially powerful approach to identifying susceptibility variants for common multifactorial diseases such as type 1 diabetes, but the results are not always consistently reproducible. The IDDM5 locus has recently been narrowed to an ∼200-kb interval on chromosome 6q25 by two independent groups. These studies demonstrated that alleles at markers in the mitogen-activating protein kinase 7 interacting protein 2 (MAP3K7IP2)/SUMO4 region were associated with susceptibility to type 1 diabetes. Subsequent studies, however, showed inconsistency in the association of the SUMO4 gene with type 1 diabetes. To clarify the contribution of the M55V polymorphism of the SUMO4 gene to type 1 diabetes susceptibility, 541 type 1 diabetic patients and 768 control subjects were studied in Asian populations. The M55V polymorphism was significantly associated with type 1 diabetes in Asian populations (summary odds ratio [OR] 1.46, P = 0.00083, Mantel-Haenszel test). Meta-analysis of published studies and the present data confirmed a highly significant association in Asian populations (summary OR 1.29, P = 7.0 × 10−6) but indicated heterogeneity in the genetic effect of the SUMO4/MAP3K7IP2 locus on type 1 diabetes among diverse ethnic groups. These data indicate that the MAP3K7IP2/SUMO4 locus in the IDDM5 interval is associated with type 1 diabetes in Asian populations.


    • Accepted September 13, 2005.
    • Received August 1, 2005.
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