Insulin Gene/IDDM2 Locus in Japanese Type 1 Diabetes: Contribution of Class I Alleles and Influence of Class I Subdivision in Susceptibility to Type 1 Diabetes

• Published in: The journal of clinical endocrinology and metabolism Vol. 92; no. 5; pp. 1791 - 1795
• Main Authors: Awata, Takuya, Kawasaki, Eiji, Ikegami, Hiroshi, Kobayashi, Tetsuro, Maruyama, Taro, Nakanishi, Koji, Shimada, Akira, Iizuka, Hiroyuki, Kurihara, Susumu, Osaki, Masataka, Uga, Miho, Kawabata, Yumiko, Tanaka, Shoichiro, Kanazawa, Yasuhiko, Katayama, Shigehiro
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Oxford University Press 01.05.2007; Endocrine Society
• Subjects: Adult; Age of Onset; Alleles; Autoimmunity; Biological and medical sciences; Diabetes; Diabetes mellitus (insulin dependent); Diabetes Mellitus, Type 1 - epidemiology; Diabetes Mellitus, Type 1 - genetics; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Fundamental and applied biological sciences. Psychology; Gene Frequency; Gene polymorphism; Genotyping; Haplotypes; Humans; Insulin; Insulin - genetics; Japan - epidemiology; Male; Medical sciences; Minisatellite Repeats - genetics; Polymorphism, Genetic - genetics; Polymorphism, Single Nucleotide - genetics; Population studies; Single-nucleotide polymorphism; Susceptibility; Vertebrates: endocrinology; Asia; Japan; Endocrinopathy; Immunopathology; Pancreatic hormone; Allele; Type 1 diabetes; Autoimmune disease; Genetics; Locus; Insulin; Endocrinology
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2006-2242

Context: It is suggested that 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 multicenter 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 variable number of tandem repeat (VNTR) class I/class III status was estimated by genotyping the −23 HphI single nucleotide polymorphism. 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 [odds ratio (OR) 0.20, P < 10−5]. The class I subdivision revealed IC to increase significantly in patients with type 1 diabetes (P = 0.002), whereas 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 the 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.