Meta-analysis of interrelation between cytotoxic T-lymphocyte antigen-4 (+49A>G) polymorphism and recurrent spontaneous abortion

The most frequent consequence of pregnancy is a miscarriage, which occurs when a pregnancy terminates before the fetus achieves viability. Fifteen percent of clinically confirmed pregnancies result in miscarriage, and overall reproductive losses are closer to 50%. The prevalence of RSA ranges from 1% to 5% of all couples attempting to conceive. Approximately, half of all recurrent miscarriages (RMs) are unexplained. The objective of this study was to explore the plausible association of cytotoxic T-lymphocyte antigen-4 (CTLA-4) +49A>G polymorphism and recurrent spontaneous abortion (RSA) susceptibility. We conducted a comprehensive search in various databases for research articles published in relation to the correlation between RSA and the CTLA-4 +49A>G polymorphism. After the initial screening of research articles, 12 studies with 3033 cases and 3273 controls were analyzed in this meta-analysis. To perform this study, we followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The strength of the correlation between the CTLA-4 +49A>G polymorphism and RSA susceptibility was evaluated by using 95% confidence intervals (CIs) and a pooled odds ratio (OR). Begger's and Egger's tests were performed to determine the publication bias. A significant association between RSA susceptibility and the CTLA-4 +49A>G polymorphism was observed in Asians in dominant (OR = 1.426, 95% CI = 1.100–1.849, P = 0.007) and additive (AG vs. AA – OR = 1.192, 95% CI = 1.019–1.393, P = 0.028) models for both fixed- and random-effects models. The findings of this meta-analysis suggest a significant association between CTLA-4 + 49A/G polymorphism and susceptibility to RSA in Asian populations in dominant and additive models.