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Evidence for the Role of Small Ubiquitin-Like Modifier 4 as a General Autoimmunity Locus in the Japanese Population

Clinical Research and Trial Center (M.T., H.S.), Department of Metabolism/Diabetes and Clinical Nutrition (E.K., A.M., K.F.), Nagasaki University Hospital of Medicine and Dentistry, Nagasaki 852-8501, Japan; First Department of Internal Medicine (H.Id., T.F., N.A., H.Y., K.E.), Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523, Japan; Clinical Research Center (K.M.), National Hospital Organization Nagasaki Medical Center, Nagasaki 856-8562, Japan; Department of Geriatric Medicine (S.N., H.Ik.), Osaka University Graduate School of Medicine, Osaka 565-0871, Japan; and Division of Endocrinology and Diabetes (T.A.), Department of Medicine, Saitama Medical School, Saitama 350-0495, Japan

Address all correspondence and requests for reprints to: Eiji Kawasaki, M.D., Ph.D., Department of Metabolism/Diabetes and Clinical Nutrition, Nagasaki University Hospital of Medicine and Dentistry, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan. E-mail: eijikawa{at}net.nagasaki-u.ac.jp.

Context: Recently, an association of a single nucleotide polymorphism, 163A>G encoding M55V, in the gene SUMO4, which has been shown to be a negative feedback regulator for nuclear factor B, has been reported in type 1 diabetes.

Objective: To establish whether SUMO4 locus contributes to the genetic susceptibility to other autoimmune disorders, a case-control analysis was carried out using genomic DNA from type 1 diabetes, autoimmune thyroid disease (AITD), rheumatoid arthritis (RA), and primary Sjögren’s syndrome.

Subjects: A total of 1480 samples, including 929 cases (411 patients with type 1 diabetes, 292 AITD, 172 RA, and 54 primary Sjögren’s syndrome) and 551 healthy control subjects of Japanese origin participated in the study.

Methods: The 163A>G (rs237025, M55V) polymorphism of SUMO4 was genotyped.

Results: SUMO4 M55V variant was associated not only with type 1 diabetes [odds ratio (OR), 1.42; 95% confidence interval (CI), 1.09–1.84; P = 0.0072], but also with increased risk of other autoimmune diseases, AITD (OR, 1.52; 95% CI, 1.14–2.03; P = 0.0041) and RA without amyloidosis (OR, 1.53; 95% CI, 1.65–2.24; P = 0.027), but not primary Sjögren’s syndrome. Furthermore, the association of SUMO4 M55V variant was stronger in type 1 diabetic patients complicated with AITD (OR, 1.62; 95% CI, 1.06–2.47; P = 0.023) and in patients who have neither type 1 diabetes-susceptible class II HLA, DRB1*0405 nor DRB1*0901 (OR, 2.28; 95% CI, 1.34–3.87; P = 0.0018).

Conclusions: These results indicate that the SUMO4 is a more common autoimmune disease gene and a supplementary risk factor to type 1 diabetes in conjunction with class II HLA.

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				S. Noso, T. Fujisawa, Y. Kawabata, K. Asano, Y. Hiromine, A. Fukai, T. Ogihara, and H. Ikegami Association of Small Ubiquitin-Like Modifier 4 (SUMO4) Variant, Located in IDDM5 Locus, with Type 2 Diabetes in the Japanese Population J. Clin. Endocrinol. Metab., June 1, 2007; 92(6): 2358 - 2362. [Abstract] [Full Text] [PDF]