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 Tsurumaru23,
- Shigetaka Sugihara4,
- Inkyu Lee5,
- Eiji Kawasaki3,
- Takuya Awata6 and
- Toshio Ogihara1
- 1Department of Geriatric Medicine, Osaka University Graduate School of Medicine, Osaka, Japan
- 2Clinical Research and Trial Center, Nagasaki University Hospital of Medicine and Dentistry, Nagasaki, Japan
- 3Department of Metabolism/Diabetes and Clinical Nutrition, Nagasaki University Hospital of Medicine and Dentistry, Nagasaki, Japan
- 4Department of Pediatrics, Tokyo Women’s Medical University Daini Hospital, Tokyo, Japan
- 5Department of Internal Medicine, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, Korea
- 6Division of Endocrinology and Diabetes, Department of Medicine, Saitama Medical School, Saitama, Japan
- 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
Abstract
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.
- MAP3K7IP2, mitogen-activating protein kinase 7 interacting protein 2
- NF-κB, nuclear factor-κB
- SNP, single nucleotide polymorphism
- TDT, transmission disequilibrium test
Footnotes
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- Accepted September 13, 2005.
- Received August 1, 2005.
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