a Department of Respiratory Medicine , The First Affiliated Hospital of Chongqing Medical University , Chongqing , China.
b Department of Respiratory Medicine , The Second Affiliated Hospital of Chongqing Medical University , Chongqing , China.
Immunol Invest. 2019 Aug;48(6):563-576. doi: 10.1080/08820139.2019.1599009. Epub 2019 May 2.
: Polymorphisms in T-cell immunoglobulin and mucin domain 3 (TIM-3) gene have been implicated in susceptibility to autoimmune diseases (ADs) with inconsistent results. The aim of this study was to perform meta-analyses for clarifying the relationship between them. : All relevant case-control studies were searched in PubMed, Embase, Wanfang, and China National Knowledge Infrastructure. Meta-analysis was conducted in the dominant and allelic models, and checked for heterogeneity and publication bias. The Odds ratio (OR) and 95% confidence interval (CI) was used to assess the strength of the associations. : Seventeen studies with four TIM-3 polymorphisms (+4259A>C, -574G>T, -1516G>T, and -1541C>T) were identified, involving 3,399 cases and 3,911 controls. TIM-3 -1516G>T polymorphism showed significant associations with ADs risk among Chinese; however, the significant finding was unstable in sensitivity analysis. In the overall population, TIM-3 + 4259A>C polymorphism demonstrated stable significant associations with ADs risk in the dominant (OR = 1.57, 95%CI = 1.13-2.18, = 0.007) and allelic (OR = 1.51, 95%CI = 1.10-2.08, = 0.01) models, and with rheumatoid arthritis (RA) risk in the dominant (OR = 2.09, 95%CI = 1.60-2.73, < 0.00001) and allelic (OR = 1.95, 95%CI = 1.51-2.51, < 0.00001) models. Cumulative meta-analyses confirmed that these significant results were robust. Concerning TIM-3 -574 G > T or -1541C>T polymorphism, no significant associations were detected. : These findings reveal that TIM-3 + 4259A>C might be a potential susceptible predictor of ADs and especially RA. Further functional and clinical investigation between these diseases and TIM-3 polymorphisms is warranted.
: T 细胞免疫球蛋白和粘蛋白域 3(TIM-3)基因中的多态性与自身免疫性疾病(ADs)的易感性有关,但结果不一致。本研究的目的是进行荟萃分析以阐明它们之间的关系。 : 在 PubMed、Embase、万方和中国知识基础设施中搜索所有相关的病例对照研究。在显性和等位基因模型中进行荟萃分析,并检查异质性和发表偏倚。使用优势比(OR)和 95%置信区间(CI)来评估关联的强度。 : 确定了 17 项研究,涉及 4 种 TIM-3 多态性(+4259A>C、-574G>T、-1516G>T 和 -1541C>T),包括 3399 例病例和 3911 例对照。TIM-3-1516G>T 多态性与中国人 ADs 风险显著相关;然而,在敏感性分析中,这一显著发现并不稳定。在总体人群中,TIM-3+4259A>C 多态性在显性(OR=1.57,95%CI=1.13-2.18, =0.007)和等位基因(OR=1.51,95%CI=1.10-2.08, =0.01)模型中与 ADs 风险显著相关,在显性(OR=2.09,95%CI=1.60-2.73, <0.00001)和等位基因(OR=1.95,95%CI=1.51-2.51, <0.00001)模型中与类风湿关节炎(RA)风险显著相关。累积荟萃分析证实了这些显著结果的稳健性。关于 TIM-3-574G>T 或 -1541C>T 多态性,未检测到显著相关性。 : 这些发现表明,TIM-3+4259A>C 可能是 ADs 尤其是 RA 的潜在易感预测因子。需要进一步研究这些疾病与 TIM-3 多态性之间的功能和临床关系。