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Diabetes 54:3582-3586, 2005
© 2005 by the American Diabetes Association, Inc.

Brief Genetics Reports

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

Shinsuke Noso1, Hiroshi Ikegami1, Tomomi Fujisawa1, Yumiko Kawabata1, Katsuaki Asano1, Yoshihisa Hiromine1, Masako Tsurumaru2,3, Shigetaka Sugihara4, Inkyu Lee5, Eiji Kawasaki3, Takuya Awata6, and Toshio Ogihara1

1 Department of Geriatric Medicine, Osaka University Graduate School of Medicine, Osaka, Japan
2 Clinical Research and Trial Center, Nagasaki University Hospital of Medicine and Dentistry, Nagasaki, Japan
3 Department of Metabolism/Diabetes and Clinical Nutrition, Nagasaki University Hospital of Medicine and Dentistry, Nagasaki, Japan
4 Department of Pediatrics, Tokyo Women’s Medical University Daini Hospital, Tokyo, Japan
5 Department of Internal Medicine, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, Korea
6 Division of Endocrinology and Diabetes, Department of Medicine, Saitama Medical School, Saitama, Japan

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 x 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.

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}geriat.med.osaka-u.ac.jp

Abbreviations: MAP3K7IP2, mitogen-activating protein kinase 7 interacting protein 2; NF-{kappa}B, nuclear factor-{kappa}B; SNP, single nucleotide polymorphism; TDT, transmission disequilibrium test


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