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)b...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:Pub Med,Embase,Google Scholar,Cochrane Libraries,and Chinese databases were searched to identify potential studies through July2021 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/A at rs1801131:OR:1.39,95%CI:1.04-1.86).For fathers,the polymorphisms of MTHFR at rs1801133 were significantly associated with risk of CHDs in the heterozygote comparisons(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),and rs2274976(G/A vs G/G:OR:0.75,95%CI:0.61-0.92),and methionine synthase reductase(MSR)at rs1801394(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 analysis yielded consistent results.No evidence of publication bias was observed.Conclusions:The present study indicates that polymorphisms of maternal MTHFR at rs1801133 and rs1801131,parental MTHFR at rs1801133,as well as children’s MTHFR at rs1801133,rs1801131 and rs2274976,and MSR at rs1801394 and rs1532268 are significantly associated with risk of CHDs.展开更多
基金supported by the Project Funded by National Key Research and Development Project(No.2018YFE0114500)National Natural Science Foundation Program of China(No.82073653 and 81803313)+5 种基金China Postdoctoral Science Foundation(No.2020M682644)Hunan Provincial Science and Technology Talent Support Project(No.2020TJ-N07)Hunan Provincial Key Research and Development Program(No.2018SK2063,No.2018SK2064)Natural Science Foundation of Hunan Province(No.2018JJ2551)Open Project from NHC Key Laboratory of Birth Defect for Research and Prevention(No.KF2020006)Science and Technology Planning Project of Guangdong Province(No.2020A1414010152)。
文摘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:Pub Med,Embase,Google Scholar,Cochrane Libraries,and Chinese databases were searched to identify potential studies through July2021 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/A at rs1801131:OR:1.39,95%CI:1.04-1.86).For fathers,the polymorphisms of MTHFR at rs1801133 were significantly associated with risk of CHDs in the heterozygote comparisons(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),and rs2274976(G/A vs G/G:OR:0.75,95%CI:0.61-0.92),and methionine synthase reductase(MSR)at rs1801394(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 analysis yielded consistent results.No evidence of publication bias was observed.Conclusions:The present study indicates that polymorphisms of maternal MTHFR at rs1801133 and rs1801131,parental MTHFR at rs1801133,as well as children’s MTHFR at rs1801133,rs1801131 and rs2274976,and MSR at rs1801394 and rs1532268 are significantly associated with risk of CHDs.
