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Awata, T. et al.

Takuya Awata, Eiji Kawasaki, Hiroshi Ikegami, Tetsuro Kobayashi, Taro Maruyama, Koji Nakanishi, Akira Shimada, Hiroyuki Iizuka, Susumu Kurihara, Masataka Osaki, Miho Uga, Yumiko Kawabata, Shoichiro Tanaka, Yasuhiko Kanazawa, Shigehiro Katayama,

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.

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.[1]

References

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. Awata, T., Kawasaki, E., Ikegami, H., Kobayashi, T., Maruyama, T., Nakanishi, K., Shimada, A., Iizuka, H., Kurihara, S., Osaki, M., Uga, M., Kawabata, Y., Tanaka, S., Kanazawa, Y., Katayama, S. J. Clin. Endocrinol. Metab. (2007) [Pubmed]

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