Association of the T-cell regulatory gene CTLA4 with Graves' disease and autoimmune thyroid disease in the Japanese
Association of the T-cell regulatory gene CTLA4 with Graves' disease and autoimmune thyroid disease in the Japanese
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DOI：
10.1007/s10038-003-0120-5
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发表时间：
2004-03-01
影响因子：
3.5
通讯作者：
Sasazuki, T
中科院分区：
文献类型：
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作者：
Furugaki, K;Shirasawa, S;Sasazuki, T
自身免疫性甲状腺疾病（AITD）是由对自身甲状腺抗原的免疫反应引起的。据报道，编码 T 淋巴细胞免疫反应负调节因子的细胞毒性 T 淋巴细胞抗原 4 (CTLA4) 基因与 AITD 相关和/或相关。最近，白种人的AITD易感性被定位到CTLA4基因的6.1-kb 3'UTR，其中三个单核苷酸多态性（SNP）CT60、JO31和JO30与AITD密切相关。为了确定日本人中 CTLA4 基因与 AITD 的关联，对 380 名 AITD 患者和 266 名健康对照者进行了 CTLA4 基因的 4 个 SNP 的病例对照关联分析。在检查的 SNP 中，SNP JO31 与日本人的 AITD 相关性最显着，而 JO30 与 AITD 的相关性则没有观察到。日本对照者JO31的疾病易感G等位基因的频率高于白种人（67.1% vs 50.2%）；然而，JO31 的 G 等位基因与日本人的格雷夫斯病 (GD)（67.1% vs 76.3%，P=0.0013）和 AITD（67.1% vs 74.2%，P=0.0055）相关。此外，在主导模型中，JO31 的 G 等位基因与 GD [P=0.0051，比值比 (OR)=1.7] 和 AITD (P=0.016，OR=1.5) 风险增加相关。这些结果表明 CTLA4 基因与日本人 GD 和 AITD 的易感性有关。
Autoimmune thyroid disease (AITD) is caused by an immune response to self-thyroid antigen. The cytotoxic T-lymphocyte antigen-4 (CTLA4) gene, encoding a negative regulator of the T-lymphocyte immune response, had been reported to be associated and/or linked to AITD. Recently, AITD susceptibility in the Caucasians was mapped to the 6.1-kb 3'UTR of the CTLA4 gene, in which the three single-nucleotide polymorphisms (SNPs) CT60, JO31, and JO30 were strongly associated with AITD. In order to determine the association of the CTLA4 gene with AITD in the Japanese, case-control association analysis for the four SNPs of the CTLA4 gene using 380 AITD patients and 266 healthy controls was done. Among the SNPs examined, the SNP JO31 was most significantly associated with AITD in the Japanese, whereas the association of the JO30 with AITD was not observed. The frequency of the disease-susceptible G allele of the JO31 of the Japanese control was higher than that of the Caucasians (67.1% vs 50.2%); however, the G allele of the JO31 was associated with Graves' disease (GD) (67.1% vs 76.3%, P=0.0013) and AITD in the Japanese (67.1% vs 74.2%, P=0.0055). Furthermore, the G allele of the JO31 was associated with the increased risk for GD [P=0.0051, odds ratio (OR)=1.7] and AITD (P=0.016, OR=1.5) in a dominant model. These results suggested that the CTLA4 gene is involved in the susceptibility for GD and AITD in the Japanese.