血清同型半胱氨酸水平和亚甲基四氢叶酸还原酶、甲硫氨酸合成酶还原酶基因多态性与胎盘缺血性疾病的相关性

Correlations between gene polymorphisms of MTHFR and MTRR,serum homocysteine level and ischemic placental disease

目的探讨孕妇血清同型半胱氨酸(homocysteine,Hcy)水平和亚甲基四氢叶酸还原酶(methylenetetrahydrmethyltransferase reductase,MTHFR)、甲硫氨酸合成酶还原酶(methyltransferase reductase,MTRR)基因多态性与胎盘缺血性疾病(ischemic placental disease,IPD)的相关性。方法选取2017年1月至2019年10月在郑州大学第三附属医院就诊并分娩的孕产妇448例,其中298例IPD孕妇为病例组,根据妊娠结局分为3个亚组:子痫前期组(135例)、胎儿生长受限(fetal growth restriction,FGR)组(90例)、胎盘早剥组(73例);另选择同期150例正常妊娠孕妇为对照组。通过循环酶法测定血清Hcy水平及qRT-PCR法检测MTHFRC677T、A1298C和MTRRA66G的基因多态性。结果(1)胎盘早剥组、FGR组、子痫前期组的血清Hcy分别为(11.00±2.58)μmol/L、(9.05±2.11)μmol/L、(10.28±2.31)μmol/L,高于对照组(6.77±1.51)μmol/L(P均<0.05)。MTHFRC677位点TT基因型携带者血清Hcy水平明显高于其他型,A1298位点CC基因型携带者血清Hcy水平明显高于AA基因型(P均<0.05),MTRRA66位点GG基因型携带者血清Hcy水平与其他型比较差异无统计学意义(P均>0.05)。(2)MTHFRC677T基因,FGR组TT型、突变T等位基因和子痫前期组CT型、突变T等位基因分布与对照组比较差异有统计学意义(P均<0.05);MTHFRA1298C基因,胎盘早剥组、子痫前期组的CC型及突变C等位基因分布与对照组比较差异有统计学意义(P均<0.05)。MTRRA66G基因型多态性与IPD无明显相关性(P均>0.05)。结论IPD患者普遍存在血清Hcy水平升高;MTHFR基因C677T、A1298C多态性均可致Hcy升高,与IPD发病关系密切,但MTRRA66G位点突变与IPD无相关性。

Objective To investigate the relationship between serum homocysteine(Hcy)and gene polymorphism of MTHFR and MTRR with ischemic placental disease(IPD).Methods A total of 448 pregnant women who gave birth at the Third Affiliated Hospital of Zhengzhou University from January 2017 to October 2019 were selected.Among them,298 pregnant women with IPD were the case group.According to the pregnancy outcome,they were divided into three subgroups:preeclampsia group(135 cases),fetal growth restriction(FGR)group(90 cases),placental abruption group(73 cases),150 normal pregnant women in the same period were selected as the control group.The gene polymorphism of MTHFRC677 T,A1298 C and MTRRA66 G in oral epithelial mucosal cells of the study subjects was detected by quantitative PCR meanwhile the level serum Hcy was tested by the enzymatic cycling assay.Results(1)The serum Hcy level in the placental abruption group,FGR group,preeclampsia group were(11.00±2.58)μmol/L、(9.05±2.11)μmol/L、(10.28±2.31)μmol/L,respectively.These were all higher than those in the control group(6.77±1.51)μmol/L(P<0.05).The serum Hcy level in the MTHFRC677 TT genotype carries was higher than those in the other genotypes carriers,the serum Hcy level in the A1298 CC genotype carries was significantly higher than that in the AA genotype carriers(P<0.05).But there was no significant difference in serum Hcy levels in the MTRRA66 GG genotype carries and the other genotypes carriers(P>0.05).(2)The frequency of TT genotype and mutant T allele in MTHFRC677 T gene of women in FGR group and CT genotype and mutant T allele of women in preeclampsia group were significantly higher than those of women in control group(P<0.05);The frequency of CC genotype and mutant C allele in MTHFRA1298 C gene of women in placental abruption and preeclampsia group were all significantly higher than those of women in control group(P<0.05).But there was no significant difference in MTRRA66 G gene polymorphism and IPD(P>0.05).Conclusion The increase of serum Hcy level is common in patients with IPD.The polymorphism of C677 T,A1298 C in MTHFR gene all can cause the increase of serum Hcy and are closely related to the pathogenesis of IPD,but the lack of association between the MTRRA66 G polymorphism and IPD.