目的探讨母亲糖尿病、解偶联蛋白2基因(UCP2)多态性及两者的交互作用与子代先天性心脏病(CHD)的关系。方法采用以医院为基础的病例对照研究,选择2018年3月至2019年8月在湖南省儿童医院确诊的464例单纯CHD患儿的母亲为病例组,选择同期住...目的探讨母亲糖尿病、解偶联蛋白2基因(UCP2)多态性及两者的交互作用与子代先天性心脏病(CHD)的关系。方法采用以医院为基础的病例对照研究,选择2018年3月至2019年8月在湖南省儿童医院确诊的464例单纯CHD患儿的母亲为病例组,选择同期住院、无先天畸形的504例患儿的母亲为对照组。通过问卷调查,收集相关暴露信息,同时采集母亲静脉血5 mL,用于UCP2基因多态性检测。采用多因素logistic回归分析探讨母亲糖尿病、UCP2基因多态性及两者交互作用与子代CHD的关联性。结果多因素logistic回归分析显示,在控制混杂因素后,患有妊娠期糖尿病(OR=2.96,95%CI:1.57~5.59)、有妊娠期糖尿病史(OR=3.16,95%CI:1.59~6.28)和妊娠前患有糖尿病(OR=4.52,95%CI:2.41~8.50)均显著增加子代CHD的风险(P<0.05)。母亲UCP2基因两个位点rs659366(T/C vs C/C:OR=1.49,95%CI:1.02~2.16;T/T vs C/C:OR=2.77,95%CI:1.67~4.62)和rs660339(A/A vs G/G:OR=2.19,95%CI:1.34~3.58)的多态性与子代CHD的风险存在关联(P<0.05)。交互作用分析显示,UCP2基因两个位点(rs659366和rs660339)的多态性与母亲糖尿病在子代CHD发生中存在交互作用(P<0.05)。结论母亲糖尿病、UCP2基因多态性及其交互作用与子代CHD发病相关。展开更多
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
文摘目的探讨母亲糖尿病、解偶联蛋白2基因(UCP2)多态性及两者的交互作用与子代先天性心脏病(CHD)的关系。方法采用以医院为基础的病例对照研究,选择2018年3月至2019年8月在湖南省儿童医院确诊的464例单纯CHD患儿的母亲为病例组,选择同期住院、无先天畸形的504例患儿的母亲为对照组。通过问卷调查,收集相关暴露信息,同时采集母亲静脉血5 mL,用于UCP2基因多态性检测。采用多因素logistic回归分析探讨母亲糖尿病、UCP2基因多态性及两者交互作用与子代CHD的关联性。结果多因素logistic回归分析显示,在控制混杂因素后,患有妊娠期糖尿病(OR=2.96,95%CI:1.57~5.59)、有妊娠期糖尿病史(OR=3.16,95%CI:1.59~6.28)和妊娠前患有糖尿病(OR=4.52,95%CI:2.41~8.50)均显著增加子代CHD的风险(P<0.05)。母亲UCP2基因两个位点rs659366(T/C vs C/C:OR=1.49,95%CI:1.02~2.16;T/T vs C/C:OR=2.77,95%CI:1.67~4.62)和rs660339(A/A vs G/G:OR=2.19,95%CI:1.34~3.58)的多态性与子代CHD的风险存在关联(P<0.05)。交互作用分析显示,UCP2基因两个位点(rs659366和rs660339)的多态性与母亲糖尿病在子代CHD发生中存在交互作用(P<0.05)。结论母亲糖尿病、UCP2基因多态性及其交互作用与子代CHD发病相关。
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.
