Evidence-based Analysis On The Associations Between Forkhead Box Protein 3 Gene（FOXP3） Polymorphisms And Susceptibility Of Preeclampsia

Objective:Pre-eclampsia（PE）is a multisystemic disease that specifically occurs in human pregnancy and seriously threatens the maternal and fetal health worldwide.The occurrence and progress of PE is the product of the combined action of multiple factors-multiple mechanisms-multiple pathways,among which genetic factors play essential roles.Recently,growing number of studies have reported the relationship of FOXP3 gene single nucleotide polymorphism（SNPs）with PE,but the results still remain greatly controversial.Therefore,the predictive value of FOXP3 gene in PE is still unclear.This study intends to further evaluate the correlation between FOXP3 gene and PE through evidence-based medical methods,looking forward to provide theoretical basis for seeking novel markers for the early diagnosis,prevention and treatment of PE.Methods:China Biology Medicine disc（CBM）,Chinese National Knowledge Infrastructure（CNKI）,Chinese Science and Technique Journals Database（VIP）,Wan Fang,Pub Med,Embase and Cochrane Library were comprehensively retrieved to obtain published investigations on the correlation between FOXP3 gene SNPs and PE.The retrieval period was up to the end of January 2022.Review Manager 5.3 software was employed to complete statistical processing and analyses.The effects of FOXP3 SNPs on the susceptibility of PE were estimated through the calculation of combined odds ratios（ORs）and corresponding 95% confidence intervals（CIs）in each genetic model.Results:Totally 8 investigations involving 3446 subjects were enrolled in the current study.It was shown that AC and（AC + CC）genotypes of FOXP3 rs3761548 were significantly related to the increased susceptibility of PE in over-dominant and recessive models（AC vs.AA + CC: OR = 1.19,95%CI = 1.02-1.38,P = 0.03;AA vs.AC + CC: OR = 0.59,95%CI: 0.36-0.97,P = 0.04）.Furthermore,FOXP3 rs2232365 polymorphism was also remarkably associated with PE susceptibility in recessive model（GG vs GA + AA: OR = 0.79,95%CI: 0.65-0.97,P = 0.03）.Moreover,the subgroup analyses further revealed the relationship between FOXP3 polymorphisms and PE susceptibility in different ethnic populations.In addition,the relationships between FOXP3 rs3761548 and rs2232365 polymorphisms and PE severity were observed in certain genetic models.However,no association of FOXP3 rs4824747rs3761547 and rs2280883 polymorphisms with PE susceptibility was found.Conclusions:The present meta-analysis further confirmed that FOXP3 rs3761548 and rs2232365 SNPs were significantly associated with PE susceptibility,which may act as potential biomarkers for early diagnosis and risk prediction of PE.