Association between T-Cell Immunoglobulin and Mucin Domain 3 (TIM-3) Genetic Polymorphisms and Susceptibility to...

Background: 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. Methods: 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. Results: 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, P = 0.007) and allelic (OR = 1.51, 95%CI = 1.10-2.08, P = 0.01) models, and with rheumatoid arthritis (RA) risk in the dominant (OR = 2.09, 95%CI = 1.60-2.73, P < 0.00001) and allelic (OR = 1.95, 95%CI = 1.51-2.51, P < 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. Conclusion: 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.