目的:母亲围孕期服用叶酸是迄今为止减少子代先天性心脏病(congenital heart disease,CHD)最有效的一级预防措施,既往研究提示其相关机制涉及基因和环境因素,但仍未阐明。本研究旨在探讨母亲围孕期服用叶酸、叶酸受体1基因(FOLR1)和叶...目的:母亲围孕期服用叶酸是迄今为止减少子代先天性心脏病(congenital heart disease,CHD)最有效的一级预防措施,既往研究提示其相关机制涉及基因和环境因素,但仍未阐明。本研究旨在探讨母亲围孕期服用叶酸、叶酸受体1基因(FOLR1)和叶酸受体2基因(FOLR2)多态性及两者的交互作用与子代CHD的关系,以期为围孕期叶酸服用剂量的个体化指导提供流行病学证据。方法:采用医院为基础的病例对照研究,招募2017年12月至2020年3月在湖南省儿童医院确诊的569例单纯性CHD患儿的母亲为病例组,以同期、该院确诊的无先天性疾病的652例正常儿的母亲为对照组。通过以问卷为基础的面对面访谈,收集母亲人口学信息和围孕期相关暴露信息,同时采集母亲静脉血5 mL用于FOLR1和FOLR2基因多态性检测。采用多因素logistic回归分析探讨母亲围孕期服用叶酸、FOLR1和FOLR2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:调整混杂因素后,围孕期服用叶酸能够显著降低子代CHD的风险[调整的相对危险比(adjusted odds ratio,aOR)=0.58,95%CI:0.35~0.95]。母亲FOLR1基因位点rs2071010(G/A vs G/G:aOR=0.67,95%CI:0.47~0.96)与子代CHD风险显著相关[P<0.05,错误发现率P值(false discovery rate P value,FDR;)<0.1];FOLR2基因位点rs514933(T/C vs T/T:aOR=0.60,95%CI:0.43~0.84;C/C vs T/T:aOR=0.55,95%CI:0.33~0.90)在显性模型[(T/C+C/C)vs T/T:aOR=0.59,95%CI:0.43~0.81]和加性模型(C/C vs T/C vs T/T:aOR=0.70,95%CI:0.56~0.88)下均与子代CHD风险显著相关(均P<0.05,FDR;<0.1)。rs2071010 G→A(aOR=0.59,95%CI:0.41~0.86)和rs514933 T→C(aOR=0.52,95%CI:0.37~0.74)与母亲围孕期服用叶酸在子代CHD发生中存在交互作用(P<0.05,FDR;<0.1)。结论:母亲携带FOLR1基因rs2071010G→A与FOLR2基因rs514933 T→C的突变型能够降低子代CHD的发生风险,且围孕期服用叶酸可以强化SNP rs2071010和SNP rs514933对子代发生CHD的保护作用。展开更多
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:母亲围孕期服用叶酸是迄今为止减少子代先天性心脏病(congenital heart disease,CHD)最有效的一级预防措施,既往研究提示其相关机制涉及基因和环境因素,但仍未阐明。本研究旨在探讨母亲围孕期服用叶酸、叶酸受体1基因(FOLR1)和叶酸受体2基因(FOLR2)多态性及两者的交互作用与子代CHD的关系,以期为围孕期叶酸服用剂量的个体化指导提供流行病学证据。方法:采用医院为基础的病例对照研究,招募2017年12月至2020年3月在湖南省儿童医院确诊的569例单纯性CHD患儿的母亲为病例组,以同期、该院确诊的无先天性疾病的652例正常儿的母亲为对照组。通过以问卷为基础的面对面访谈,收集母亲人口学信息和围孕期相关暴露信息,同时采集母亲静脉血5 mL用于FOLR1和FOLR2基因多态性检测。采用多因素logistic回归分析探讨母亲围孕期服用叶酸、FOLR1和FOLR2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:调整混杂因素后,围孕期服用叶酸能够显著降低子代CHD的风险[调整的相对危险比(adjusted odds ratio,aOR)=0.58,95%CI:0.35~0.95]。母亲FOLR1基因位点rs2071010(G/A vs G/G:aOR=0.67,95%CI:0.47~0.96)与子代CHD风险显著相关[P<0.05,错误发现率P值(false discovery rate P value,FDR;)<0.1];FOLR2基因位点rs514933(T/C vs T/T:aOR=0.60,95%CI:0.43~0.84;C/C vs T/T:aOR=0.55,95%CI:0.33~0.90)在显性模型[(T/C+C/C)vs T/T:aOR=0.59,95%CI:0.43~0.81]和加性模型(C/C vs T/C vs T/T:aOR=0.70,95%CI:0.56~0.88)下均与子代CHD风险显著相关(均P<0.05,FDR;<0.1)。rs2071010 G→A(aOR=0.59,95%CI:0.41~0.86)和rs514933 T→C(aOR=0.52,95%CI:0.37~0.74)与母亲围孕期服用叶酸在子代CHD发生中存在交互作用(P<0.05,FDR;<0.1)。结论:母亲携带FOLR1基因rs2071010G→A与FOLR2基因rs514933 T→C的突变型能够降低子代CHD的发生风险,且围孕期服用叶酸可以强化SNP rs2071010和SNP rs514933对子代发生CHD的保护作用。
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.
