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Submitted on October 13, 2006
Accepted on February 22, 2007
Division of Endocrinology and Diabetes, Department of Medicine (T.A., S.Ku., M.O., S.Ka.) and Division of RI Laboratory, Biomedical Research Center (T.A., H.I.), Saitama Medical University, Saitama, Japan; Department of Metabolism/ Diabetes and Clinical Nutrition (E.K., M.U.), Nagasaki University Hospital of Medicine and Dentistry, Nagasaki, Japan; Department of Endocrinology, Diabetes and Metabolism (H.K., Y.Kaw.), Kinki University School of Medicine, Osaka, Japan; Third Department of Internal Medicine (T.K., S.T.), Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan; Department of Internal Medicine (T.M.), Saitama Social Insurance Hospital, Saitama, Japan; Department of Endocrinology and Metabolism (K.N.), Toranomon Hospital, Tokyo, Japan; Department of Internal Medicine (A.S., Y.Kan.), Keio University School of Medicine, Tokyo, Japan
* To whom correspondence should be addressed. E-mail: awata{at}saitama-med.ac.jp.
Context: It is suggested insulin autoimmunity plays an important role in the development of type 1 diabetes in humans. However, the association between insulin gene (INS) region (IDDM2) and type 1 diabetes has been uncertain in Asians.
Objective: A multi-center collaboration study was conducted to clarify the role of the IDDM2 region in Japan.
Subjects and Methods: In total, 661 patients with type 1 diabetes and 706 control subjects were enrolled. The INS VNTR class I/class III status was estimated by genotyping the -23 HphI SNP. From surrounding polymorphisms across the insulin gene, we also inferred haplotypes bearing INS VNTR lineages.
Results: The frequency of the class I allele was 99.3% in patients and 96.7% in controls (P <10-5), and the class I/III or III/III genotype was found in 1.4% of patients and in 6.4% of controls (OR 0.20, P <10-5). The class I subdivision revealed IC to significantly increase in patients with type 1 diabetes (P =0.002) while ID did not; the distribution of IC and ID was significantly different between patients and controls (P =0.014).
Conclusion: The present study certainly shows that the IDDM2 region is also a susceptibility locus in Japanese population. Furthermore, it was revealed that IC may be more susceptible to type 1 diabetes than ID, which could be evidence that the INS VNTR itself confers susceptibility to type 1 diabetes.
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