The CTLA-4 gene region of chromosome 2q33 is linked to, and associated with, type 1 diabetes
The CTLA-4 gene region of chromosome 2q33 is linked to, and associated with, type 1 diabetes
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DOI：
10.1093/hmg/5.7.1075
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发表时间：
1996-07-01
影响因子：
3.5
通讯作者：
Todd, JA
中科院分区：
文献类型：
--
作者：
Nistico, L;Buzzetti, R;Todd, JA
对自身免疫性胰岛素依赖性（1型）糖尿病的易感性由环境和遗传因素的组合确定，其中包括染色体6P21（IDDM1）上MHC基因的变化，以及在11p15（IDDM2）上的胰岛素基因（IDDM1）和胰岛素基因。但是，与IDDM1和IDDM2的联系无法解释家庭中1型糖尿病的聚类，并且推断出其他基因的作用。在本报告中，我们描述了1型糖尿病与CTLA-4基因（细胞毒性T淋巴细胞相关-4）的连锁和关联，在2q33染色体上（指定的IDDM12）。 CTLA-4是T细胞介导的自身免疫性疾病的强大候选基因，因为它编码了介导T细胞凋亡的T细胞受体，并且是T细胞激活的重要负调节剂。此外，我们还提供了证据表明CTLA-4与对Graves疾病的易感性有关，Graves疾病是另一种特定器官特定的自身免疫性疾病。
Susceptibility to autoimmune insulin-dependent (type 1) diabetes mellitus is determined by a combination of environmental and genetic factors, which include variation in MHC genes on chromosome 6p21 (IDDM1) and the insulin gene on chromosome 11p15 (IDDM2). However, linkage to IDDM1 and IDDM2 cannot explain the clustering of type 1 diabetes in families, and a role for other genes is inferred. In the present report we describe linkage and association of type 1 diabetes to the CTLA-4 gene (cytotoxic T lymphocyte associated-4) on chromosome 2q33 (designated IDDM12). CTLA-4 is a strong candidate gene for T cell-mediated autoimmune disease because it encodes a T cell receptor that mediates T cell apoptosis and is a vital negative regulator of T cell activation. In addition, we provide supporting evidence that CTLA-4 is associated with susceptibility to Graves' disease, another organ-specific autoimmune disease.