摘要Background Aims:To summarize the epidemiologic evidence on the association between single nucleotide polymorphisms(SNPs)of folate metabolism genes from parents and children and risk of congenital heart diseases(CHDs)by a comprehensive systematic review and meta-analysis.Methods and results:PubMed,Embase,Google Scholar,Cochrane Libraries,and Chinese databases were searched to identify potential studies through July 2021 For mothers,the polymorphisms of Methylenetetrahydrofolate Reductase(MTHFR)at rs1801133 and rs1801131 were significantly associated with risk of CHDs in the homozygote comparisons(T/T vs C/C at rs1801133:OR:1.50,95％CI:1.31-1.71;C/C vs A/Aatrs1801131:OR:1.39,95％CI:1.04-1.86).For fathers,the polymorphisms of MTHFR at rs 1801133 were significantly associated with risk of CHDs in the heterozygote com-parisons(C/T vs C/C∶OR∶1.26,95％CI∶1.04-1.53).For children,the polymorphisms of MTHFR at rs1801133(T/T vs C/C∶OR∶2.05,95％CI∶1.57-2.66),rs1801131(A/C vs A/A∶OR∶1.32,95％CI∶1.06-1.63),andrs2274976(G/A vs G/G∶OR∶0.75,95％CI∶0.61-0.92),and methionine synthase reductase(MSR)at rs 1801394(G/G vs A/A∶OR∶1.85,95％CI∶1.21-2.85)and rs1532268(T/T vs C/C∶OR∶2.44,95％CI∶1.15-5.21;C/T vs C/C∶OR∶1.53,95％CI∶1.11-2.10).This review also assessed the risk of specific CHD subtypes associated with folate metabolism gene SNPs of children.Relevant heterogeneity moderators have been identified by subgroup analysis.Sensitivity analy-sis yielded consistent results.No evidence of publication bias was observed.Conclusions:The present study indi-cates that polymorphisms of maternal MTHFR at rs 1801133 andrs1801131,parental MTHFR at rs 1801133,as well as children's MTHFR at rs1801133,rs1801131 and rs2274976,and MSR at rs1801394 and rs1532268 are signifi-cantly associated with risk of CHDs.