Yanagawa T, Taniyama M, Enomoto S, Gomi K, Maruyama H, Ban Y, Saruta T
Department of Medicine, Nerima General Hospital, Tokyo, Japan.
Thyroid. 1997 Dec;7(6):843-6. doi: 10.1089/thy.1997.7.843.
Susceptibility to Graves' disease (GD) is determined by environmental and genetic factors. The genetic susceptibility to GD is conferred by genes in the human leukocyte antigen (HLA), and several other genes unlinked to HLA are thought to contribute to the development of GD. Three recent papers described the association of GD with the CTLA-4 gene. CTLA-4 is a candidate gene for T-cell mediated autoimmune diseases because it is a negative regulator of T-cell proliferation. As CTLA-4 association with GD may be influenced by the racial composition of the population, it is important to study it in other ethnic groups. We investigated the distribution of CTLA-4 gene polymorphism in 153 Japanese patients with GD (35 males and 118 females) and 200 controls (96 males and 104 females). An A/G transition at position 49 of exon 1 was analyzed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The distribution of genotype frequencies differs between GD and controls (chi2 = 9.46, 2 degrees of freedom, p < 0.01). The presence of at least one G allele (GG or AG) conferred an odds ratio of 2.64 (95% CI = 1.92-3.36). The present study supported the association of the CTLA-4 gene with GD in Japanese and showed that the CTLA4 gene could be one of the non-HLA linked susceptibility genes for GD.
格雷夫斯病（GD）的易感性由环境和遗传因素决定。GD的遗传易感性由人类白细胞抗原（HLA）中的基因赋予，并且一些与HLA不连锁的其他基因也被认为与GD的发生有关。最近的三篇论文描述了GD与CTLA-4基因的关联。CTLA-4是T细胞介导的自身免疫性疾病的候选基因，因为它是T细胞增殖的负调节因子。由于CTLA-4与GD的关联可能受人群种族构成的影响，在其他种族群体中进行研究很重要。我们调查了153例日本GD患者（35例男性和118例女性）和200例对照（96例男性和104例女性）中CTLA-4基因多态性的分布。通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法分析外显子1第49位的A/G转换。GD组和对照组基因型频率分布不同（χ2 = 9.46，自由度为2，p < 0.01）。至少存在一个G等位基因（GG或AG）的比值比为2.64（95%CI = 1.92 - 3.36）。本研究支持CTLA-4基因与日本人群中GD的关联，并表明CTLA4基因可能是GD的非HLA连锁易感基因之一。
