母亲MTR基因多态性与先天性心脏病易感性关联

Association of maternal MTR gene polymorphism with offspring congenital heart disease:a case-control study

目的研究母亲甲硫氨酸合成酶(MTR)基因多态性与子代先天性心脏病(CHD)间的关联性。方法于2017年11月—2019年12月在湖南省儿童医院心胸外科采用病例对照研究方法,在464例CHD患儿母亲和504例健康儿童母亲中,利用MassArray飞行时间质谱技术对MTR基因的单核苷酸多态性(SNPs)进行检测,采用SPSS24.0和Haploview软件分析MTR基因SNPs及其单倍型与CHD的关联。结果rs1266164(TT vs.CC:aOR=3.39,95%CI=1.48~7.76;隐性模型:aOR=3.27,95%CI=1.44~7.45),rs3768139(CC vs.GG:aOR=0.26,95%CI=0.11~0.58;显性模型:aOR=0.29,95%CI=0.13~0.65;隐性模型:aOR=0.62,95%CI=0.45~0.85),rs1050993(隐性模型:aOR=0.59,95%CI=0.42~0.82),rs6668344(显性模型:aOR=1.55,95%CI=1.12~2.16),rs3820571(GG vs.CC:aOR=0.28,95%CI=0.12~0.64;隐性模型:aOR=0.56,95%CI=0.40~0.79)等5个位点与子代CHD的发生存在关联。TT和CT单倍型(rs6668344-rs3754255),AGTA单倍型(rs1805087-rs2275565-rs1266164-rs4659743)以及AT和GT单倍型(rs1050993-rs6676866)与CHD的发生相关。结论MTR基因多态性与子代CHD的患病存在关联,且其单倍型影响CHD的发生。

Objective To explore the association between maternal methionine synthase(MTR)gene polymorphism and the risk of congenital heart disease(CHD)in offsprings.Methods A case-control study was conducted among 464 biological mothers of CHD children and 504 biological mothers of healthy children in the Department of Cardiothoracic Surgery,Hunan Children’s Hospital from November 2017 to December 2019.Single nucleotide polymorphisms(SNPs)of MTR gene was detected with MassArray time-of-flight mass spectrometry.The association between MTR SNPs and offspring CHD was analyzed with SPSS 24.0 software,and Haploview software was used in haplotype analysis.Results The results of multivariate logistic regression analysis demonstrated that the SNPs of following MTR gene loci were significantly associated with increased risk of CHD incidence:rs1266164(TT vs.CC:adjusted odds ratio[aOR]=3.39,95%confidence interval[95%CI]:1.48-7.76;recessive model:aOR=3.27,95%CI:1.44-7.45)and rs6668344(dominant model:aOR=1.55,95%CI:1.12-2.16);the results also revealed that SNPs of three MTR gene loci correlated with decreased risk of offspring CHD incidence included rs3768139(CC vs.GG:aOR=0.26,95%CI:0.11-0.58;dominant model:aOR=0.29,95%CI:0.13-0.65;recessive model:aOR=0.62,95%CI:0.45-0.85),rs1050993(recessive model:aOR=0.59,95%CI:0.42-0.82),and rs3820571(GG vs.CC:aOR=0.28,95%CI:0.12-0.64;recessive model:aOR=0.56,95%CI:0.40-0.79).The haplotype TT and CT of rs6668344-rs3754255,AGTA of rs1805087-rs2275565-rs1266164-rs4659743,as well as AT and GT of rs1050993-rs6676866 were associated with the incidence risk of offspring CHD.Conclusion Both the polymorphism and haplotype of maternal MTR gene might be associated with the incidence risk of offspring CHD.