MTHFR基因多态性与血清叶酸水平对妊 娠期 糖尿病患者及其妊娠结局的影响  

Effects of MTHFR gene polymorphism and serum folic acid level on pregnant women with gestational diabetes mellitus and their pregnancy outcomes

作　　者：方建红 张淑红 徐敏 杨燕 卢伟 Fang Jianhong;Zhang Shuhong;Xu Min;Yang Yan;Lu Wei(Department of Obstetrics,Qingdao Chengyang People′s Hospital,Qingdao 266109,Shandong Province,China)

机构地区：[1]青岛市城阳人民医院产科,266109

出　　处：《中华妇幼临床医学杂志（电子版）》2021年第3期291-297,共7页Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition)

基　　金：国家卫生计生委医药卫生科技发展研究中心资助项目(W2015CAE169);国家自然科学基金项目(8140289);青岛市2015年度城阳区民生科技发展计划项目(青城科字〔2015〕25号)。

摘　　要：目的探讨亚甲基四氢叶酸还原酶(MTHFR)基因多态性与血清叶酸水平,对妊娠期糖尿病(GDM)患者及其妊娠结局的影响。方法选择2016年12月至2018年12月,于青岛市城阳人民医院进行产前检查的568例GDM患者为研究对象,并将其纳入GDM组。选择同期在该院进行产前检查的674例健康孕妇纳入对照组。采用荧光定量聚合酶链反应(fqPCR)技术,分析所有受试者MTHFR基因C677T、A1298C位点基因型,同时检测其血清叶酸水平。采用χ^(2)检验,对2组受试者MTHFR基因C677T及A1298C位点等位基因及基因型分布,以及不同妊娠结局GDM孕妇C677T位点基因型分布进行比较;采用t检验、单因素方差分析及最小显著性差异(LSD)-t检验,比较不同妊娠结局GDM患者血清叶酸水平,对2组MTHFR基因C667T位点3个基因型受试者的血清叶酸水平进行组内及组间比较;采用受试者工作特征(ROC)曲线,对C667T位点不同基因型联合血清叶酸水平,对于GDM预测价值进行分析。本研究遵循的程序经青岛市城阳人民医院伦理委员会批准[审批文号:(2015年)伦理批第(11)号],并与所有受试者签署研究知情同意书。结果①GDM组受试者MTHFR基因C667T位点等位基因C的频率显著高于对照组(70.9%vs 61.5%,χ^(2)=24.483、P<0.001),该位点基因型以CC为主,而对照组则以CT为主。2组受试者MTHFR基因A1298C位点的等位基因(A/C)及基因型(AA/AC/CC)分布比较,差异均无统计学意义(均为P>0.05),并且2组均以A等位基因及AA基因型为主。②2组均为MTHFR基因C667T位点为CC、CT、TT 3种基因型受试者的血清叶酸水平比较,差异有统计学意义(P<0.05),其中CC基因型受试者血清叶酸水平显著高于TT基因型者,并且差异有统计学意义(P<0.001)。③GDM组MTHFR基因C667T位点为CC、CT及TT基因型受试者的血清叶酸水平为(16.4±2.4)nmoL/L、(14.6±3.8)nmoL/L及(12.4±3.1)nmoL/L,均显著低于对照组的(20.4±2.5)nmoL/L、(18.5±3.4)nmoL/L及Objective To investigate effects of methyleneterahydrofolate reductase(MTHFR)gene polymorphism and serum folic acid level on pregnant women with gestational diabetes mellitus(GDM)and their pregnancy outcomes.Methods A total of 568 pregnant women with GDM who underwent prenatal examination in Qingdao Chengyang People′s Hospital from December 2016 to December 2018 were selected as research objects,and they were included into GDM group.A total of 674 healthy pregnant women who underwent prenatal examination in the same period and same hospital were included into control group.Genotypes at locus C677T and A1298C of MTHFR gene in all subjects were analyzed by fluorescent quantitative polymerase chain reaction(fqPCR),meanwhile,their serum folic acid levels were detected.The alleles and genotype distributions of C677T and A1298C loci of MTHFR gene between two groups,also genotype distribution of C677T locus between pregnant women with different pregnancy outcomes in GDM group were compared by chi-square test.Serum folic acid levels between pregnant women with different pregnancy outcomes in GDM group were compared by independent-samples t test,one-way ANOVA and least significant difference(LSD)-t test were used to compare serum folic acid levels of subjects with 3 genotypes of MTHFR gene C667T loci within and between two groups.The predictive value of GDM through different genotypes of C667T locus combined with serum folic acid level were analyzed by receiver operating characteristics(ROC)curve.The procedures followed in this study were approved by the Ethics Committee of Qingdao Chengyang People′s Hospital[Approval No.(2015)Ethics Lot No.(11)].All subjects signed the informed consents.Results①The frequency of allele C at C667T locus of MTHFR gene in GDM group was significantly higher than that in control group(70.9%vs 61.5%,χ^(2)=24.483,P<0.001),and the genotype of this locus was mainly CC,while that of control group was mainly CT.There were no significant differences in distribution of alleles(A/C)and genotypes

关 键 词：亚甲基四氢叶酸还原酶(NADPH) 多态现象 遗传 糖尿病 妊娠 叶酸 妊娠结局 孕妇 

分 类 号：R714.256[医药卫生—妇产科学]