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Genetic Association between the Interleukin-2 Receptor- Gene and Mode of Onset of Type 1 Diabetes in the Japanese Population

Department of Metabolism/Diabetes and Clinical Nutrition (E.K., M.U.), Nagasaki University Hospital of Medicine and Dentistry, Nagasaki 852-8501, Japan; Division of Endocrinology and Diabetes (T.A., S.K.), Department of Medicine, Saitama Medical School, Saitama 350-0495, Japan; Department of Endocrinology, Metabolism, and Diabetes (H.I., Y.Kaw.), Kinki University School of Medicine, Osaka 589-8511, Japan; Third Department of Internal Medicine (T.K., S.T.), Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi 409-3898, Japan; Department of Internal Medicine (T.M.), Saitama Social Insurance Hospital, Saitama 330-0074, Japan; Department of General Internal Medicine and Metabolism (K.N.), Toranomon Hospital, Tokyo 105-8470, and Department of Internal Medicine (A.S., Y.Kan.), Keio University School of Medicine, Tokyo 160-8582, Japan; and The First Department of Internal Medicine (K.E.), Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523, 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}nagasaki-u.ac.jp.

Context/Objective: The IL-2 receptor- (IL2RA), also known as CD25, is expressed on the regulatory T cells, which play an important role in the control of immune responses and the maintenance of immune homeostasis. Our objective was to determine whether variants in the IL2RA gene are associated with type 1 diabetes in the Japanese population.

Design/Patients: We genotyped the four single-nucleotide polymorphisms (rs706778, rs3118470, ss52580101, and rs11594656) of the IL2RA in 885 patients with type 1 diabetes and 606 control subjects of Japanese origin. The allele and genotype frequencies were examined in the patient groups stratified by their mode of onset in a case-control study.

Results: We found evidence of association with acute-onset, but not slow-onset and fulminant, type 1 diabetes for two of the four single-nucleotide polymorphisms genotyped (rs706778 and rs3118470). The rs706778 A allele and the rs3118470 G allele were associated with an increased disease risk [odds ratio (OR) for rs706778 AA genotype 1.54, P = 4.2 x 10^–4 and OR for rs3118470 GG genotype 1.50, P = 0.0019, respectively]. Furthermore, the A-G haplotype was associated with increased type 1 diabetes risk in the acute-onset form (OR 1.30, P = 0.002).

Conclusions: The present data confirm the type 1 diabetes association with IL2RA and provide evidence that the different contributions of the IL2RA in the susceptibility to acute-onset and other forms of type 1 diabetes in the Japanese population.