Genetic susceptibility of childhood type 1 diabetes mellitus in Japan.
Genetic susceptibility of childhood type 1 diabetes mellitus in Japan.
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发表时间：
2012-10
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通讯作者：
S. Sugihara
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作者：
S. Sugihara
大多数1型糖尿病（T1 DM）是由自身免疫反应引起的，涉及遗传和环境因素，最终破坏产生胰岛素的胰腺β细胞。几个基因，包括编码人类白细胞抗原（HLA）II类（IDDM 1基因座），胰岛素（IDDM 2基因座）和细胞毒性T淋巴细胞抗原（CTLA）4（IDDM 12基因座）的基因，参与了这一过程。在本文中，我回顾了日本儿童1A型糖尿病（T1 ADM）患者的研究，包括由日本儿童和青少年糖尿病胰岛素治疗研究小组（JSGIT）进行的多中心研究的结果。JSGIT研究分析了日本儿童T1 ADM患者的HLA-DRB 1、DQB 1、DPB 1、A、C和B基因，以确定日本个体特异性的候选基因。其中一些基因也与高加索人的糖尿病有关。亲本和同胞的比较表明，几个易感DRB 1-DQB 1单倍型和抗性等位基因参与T1 ADM的发展。然而，传递不平衡试验的结果表明，在日本患者中没有HLA I类或II类基因的基因组印记。DRB 1 *09：01等位基因在2-5岁发病的患者中的频率显著高于其他患者。识别HLA基因多态性可能有助于研究抗原呈递分子结构与自身抗原肽之间的关系。JSGIT的研究还确定了HLA以外基因的单核苷酸多态性。了解与T1 ADM相关的遗传因素有助于解释日本人比高加索人发病率低的原因，将有助于我们阐明其发病机制。
Most cases of type 1 diabetes mellitus (T1DM) are caused by an autoimmune reaction, involving genetic and environmental factors, which ultimately disrupt insulin-producing pancreatic beta cells. Several genes, including those encoding human leukocyte antigen (HLA) class II (IDDM1 locus), insulin (IDDM2 locus), and cytotoxic T lymphocyte antigen (CTLA) 4 (IDDM12 locus), are involved in this process. In this paper, I review the studies of Japanese patients with childhood type 1A diabetes mellitus (T1ADM), including the results of the multicenter study conducted by The Japanese Study Group of Insulin Therapy for Childhood and Adolescent Diabetes (JSGIT). The JSGIT study analyzed the HLA-DRB1, DQB1, DPB1, A, C, and B genes in Japanese patients with childhood T1ADM to identify candidate genes specific for Japanese individuals. Some of the genes were also involved in diabetes in Caucasian. A comparison of parents and siblings showed that several susceptible DRB1-DQB1 haplotypes and resistant alleles were involved in the development of T1ADM. However, results of transmission disequilibrium tests demonstrated no genomic imprinting of HLA Class I or II genes in Japanese patients. The frequency of the DRB1*09:01 allele was significantly higher in patients who developed the disease at 2-5 years old than in other patients. Identifying HLA gene polymorphisms may help to examine the relationship between antigen-presenting molecule structures and autoantigenic peptides. The JSGIT study also identified single nucleotide polymorphisms in genes other than HLA. Understanding the genetic factors associated with T1ADM that help explain the lower incidence of this disease in Japanese than in Caucasian individuals, will help us to elucidate its pathogenesis.