Wang Ke, Zhu Qin, Lu Yunjie, Lu Hao, Zhang Feng, Wang Xuehao, Fan Ye
Key Laboratory on Living Donor Liver Transplantation, Ministry of Health, Department of Liver Surgery, First Affiliated Hospital of Nanjing Medical University , Nanjing, P.R. China .
Genet Test Mol Biomarkers. 2017 Apr;21(4):222-227. doi: 10.1089/gtmb.2016.0335. Epub 2017 Feb 17.
Cytotoxic T lymphocyte antigen-4 (CTLA-4) plays a pivotal role in immune homeostasis. Dysregulated expression of CTLA-4 leads to many autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, and type 1 diabetes (T1D). There has been a controversial association between the CTLA-4 +49 G/A SNP (rs231775) and autoimmune diseases. Therefore, this meta-analysis was performed to assess the link between rs231775 and autoimmune disease risk.
We retrieved the available studies from PUBMED and EMBASE through February, 2016 and then performed meta-analyses that included all populations, as well as by ethnicity.
After evaluating data from 4732 patients and 6270 healthy controls that included both Caucasian and Asian ethnicities, we found that rs231775 is strongly associated with autoimmune disease incidence in a homozygote comparison (GG vs. AA, 95% confidence interval [95% CI] 1.382-2.401), in a heterozygote comparison (AG vs. AA, 95% CI 1.151-1.611), in an allelic model (T allele vs. G allele, 95% CI 1.109-1.441), in a dominant model (GG/AG vs. AA, 95% CI 1.220-1.787), and in a recessive model (GG vs. AA/AG, 95% CI 1.128-1.661). The OR (odds ratio) from all models suggested a very significant association between rs231775 and autoimmune diseases.
Our present study indicates that CTLA-4 +49 G/A (rs231775) is associated with the susceptibility of autoimmune disease. Hence, rs231775 might be utilized as a diagnostic biomarker in both Asian and Caucasian populations.
细胞毒性T淋巴细胞抗原4（CTLA - 4）在免疫稳态中起关键作用。CTLA - 4表达失调会导致许多自身免疫性疾病，包括类风湿性关节炎、系统性红斑狼疮和1型糖尿病（T1D）。细胞毒性T淋巴细胞抗原4 +49 G/A单核苷酸多态性（rs231775）与自身免疫性疾病之间的关联一直存在争议。因此，进行了这项荟萃分析以评估rs231775与自身免疫性疾病风险之间的联系。
我们检索了截至2016年2月来自PUBMED和EMBASE的现有研究，然后进行了荟萃分析，包括所有人群以及按种族进行的分析。
在评估了来自包括白种人和亚洲人种的4732例患者和6270例健康对照的数据后，我们发现rs231775在纯合子比较（GG与AA，95%置信区间[95%CI] 1.382 - 2.401）、杂合子比较（AG与AA，95%CI 1.151 - 1.611）、等位基因模型（T等位基因与G等位基因，95%CI 1.109 - 1.441）、显性模型（GG/AG与AA，95%CI 1.220 - 1.787）和隐性模型（GG与AA/AG，95%CI 1.128 - 1.661）中均与自身免疫性疾病发病率密切相关。所有模型的优势比（OR）均表明rs231775与自身免疫性疾病之间存在非常显著的关联。
我们目前的研究表明，CTLA - 4 +49 G/A（rs231775）与自身免疫性疾病的易感性相关。因此，rs231775可能被用作亚洲和白种人群的诊断生物标志物。
