Orthopaedics Department, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University, No.600, Yishan Road, Shanghai, 200233, People's Republic of China.
Mol Biol Rep. 2013 Mar;40(3):2627-31. doi: 10.1007/s11033-012-2349-6. Epub 2012 Dec 20.
Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is an important molecule in the regulation of T cells, so the CTLA-4 gene has been considered as a strong candidate associated with T cell-mediated autoimmune diseases such as rheumatoid arthritis (RA). CTLA-4 has many variants and polymorphic forms, among which the +49A/G polymorphism, causing a non-synonymous substitution, has been studied most. However, previous studies of the association between the +49A/G polymorphism of the CTLA-4 gene and RA have provided conflicting results. The aim of this study was to determine the potential relationship of the CTLA-4 +49A/G polymorphism and the risk of RA in Chinese Han population. TaqMan assay was used to genotype the +49A/G polymorphism in 1,489 RA patients and 1,200 healthy controls. Furthermore, a meta-analysis of all studies relating this polymorphism in Chinese population to the risk of RA was performed. The genotype and allele frequencies of the CTLA-4 +49A/G in patients with RA differed significantly from those of controls (P = 0.03 and P = 0.007, respectively). The meta-analysis also revealed that the CTLA-4 +49G allele was associated with an increased risk of RA in Chinese population. Our results suggested that the CTLA-4 gene might contribute to the pathogenesis of RA, and the +49A/G polymorphism of this gene was a risk factor associated with increased RA susceptibility in Chinese Han population.
细胞毒性 T 淋巴细胞相关抗原 4（CTLA-4）是调节 T 细胞的重要分子，因此 CTLA-4 基因被认为是与类风湿关节炎（RA）等 T 细胞介导的自身免疫性疾病相关的强候选基因。CTLA-4 有许多变体和多态形式，其中研究最多的是非同义替换引起的+49A/G 多态性。然而，以前关于 CTLA-4 基因+49A/G 多态性与 RA 之间关联的研究结果存在争议。本研究旨在确定 CTLA-4+49A/G 多态性与中国汉族人群 RA 易感性的潜在关系。TaqMan 分析用于对 1489 例 RA 患者和 1200 例健康对照者的+49A/G 多态性进行基因分型。此外，还对所有与中国人群该多态性相关的 RA 风险的研究进行了荟萃分析。RA 患者 CTLA-4+49A/G 的基因型和等位基因频率与对照组有显著差异（P=0.03 和 P=0.007）。荟萃分析还表明，CTLA-4+49G 等位基因与中国人群 RA 的发病风险增加相关。我们的结果表明，CTLA-4 基因可能参与 RA 的发病机制，该基因的+49A/G 多态性是中国汉族人群 RA 易感性增加的一个危险因素。
