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
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
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DOI：
10.1210/jc.2006-2242
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发表时间：
2007-05-01
影响因子：
5.8
通讯作者：
Katayama, Shigehiro
中科院分区：
文献类型：
--
作者：
Awata, Takuya;Kawasaki, Eiji;Katayama, Shigehiro
背景：研究表明胰岛素自身免疫在人类1型糖尿病的发生发展中起着重要作用。然而，胰岛素基因（INS）区域（IDDM 2）和1型diabetes.Objective之间的关联一直不确定在亚洲人：一个多中心的协作研究，以澄清IDDM 2区域在日本的作用。主题和方法：在总数中，661例1型糖尿病患者和706名对照组被招募。通过对-3 HphI单核苷酸多态性进行基因分型，估计INS串联重复序列（VNTR）I类/III类状态。从胰岛素基因周围的多态性，我们还推断了具有INS VNTR谱系的单倍型。Ⅰ类等位基因频率在患者组和对照组分别为99.3%和96.7（P < 10（-5）），1.4%的患者和6.4%的对照者存在I/III或III/III类基因型[比值比（OR）0.20，P < 10（-5）]。I类细分显示IC在1型糖尿病患者中显著增加（P = 0.002），而ID没有; IC和ID的分布在患者和对照组之间存在显著差异（P = 0.014）。结论：本研究确实表明IDDM 2区域也是日本人群的易感位点。此外，还发现IC可能比ID更易患1型糖尿病，这可能是INS VNTR本身赋予1型糖尿病易感性的证据。
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 -3 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.