Gene polymorphism associated with FOXP3, CTLA-4 and susceptibility to pre-eclampsia: a meta-analysis and trial sequential analysis

Abstract

Previous studies have detected the correlation of polymorphisms in regulatory T cells associated genes FOXP3 and CTLA-4 with pre-eclampsia (PE) risk, but the results are inconsistent among studies. Eligible studies were retrieved in several database. Odds ratios (ORs) with 95% confidence intervals (CIs) were utilised to evaluate the relationship between FOXP3 rs3761548, FOXP3 rs2232365, CTLA-4 rs231775 polymorphisms, and PE susceptibility in the genetic models. The subgroup analysis and trial sequential analysis were performed. Twelve studies with a total of 4658 participants were included. There was a statistically significant association between FOXP3 rs3761548 polymorphism and PE within the recessive model in Asian (OR = 0.54, 95% CI = 0.34–0.86). Trial sequential analysis indicated sufficient proof of such association in the Asian population. This meta-analysis provides sufficient statistical evidence indicating an association between FOXP3 rs3761548 polymorphism and PE risk in Asian. IMPACT STATEMENT What is already known on this subject? FOXP3 and CTLA4 are markers of regulatory T cells which play a crucial role during a preeclamptic pregnancy. What do the results of this study add? Eleven studies with a total of 4658 participants were included. There was a statistically significant association between FOXP3 rs3761548 polymorphism and pre-eclampsia (PE) within the recessive model in Asian (OR = 0.54, 95% CI = 0.34–0.86). Trial sequential analysis indicated sufficient proof of such association in the Asian population. However, there was no enough evidence could proof significant association between FOXP3 rs2232365 or CTLA-4 rs231775 polymorphism and PE. What are the implications of these findings for clinical practice and/or further research? This meta-analysis provides sufficient statistical evidence indicating an association between FOXP3 rs3761548 polymorphism and PE risk in Asian. The findings in this study may provide a basis for the further study on FOXP3 rs3761548 polymorphism in future research.