荆州地区同型半胱氨酸及其代谢酶基因多态性与不良孕产史之间的关系

Association of homocysteine and its related gene polymorphisms with adverse pregnancy history in Jingzhou

目的探讨亚甲基四氢叶酸还原酶(5,10-Methylenetetrahydrofolate reductase,MTHFR)和甲硫氨酸合成酶还原酶(Methionine synthase reductase,MTRR)基因多态性及血浆同型半胱氨酸(Homocysteine,Hcy)水平与不良孕产史之间的关系。方法采用病例对照研究方法,收集有不良孕产史的孕妇100名做为病例组,同时选取无不良孕产史的孕妇100名做为对照组。采用Taqman-MGB技术检测口腔黏膜上皮细胞MTHFR基因C677T,A1298C和MTRR基因A66G位点基因多态性;循环酶法测定血浆Hcy浓度。结果200名孕妇中,MTHFR基因C677T位点T等位基因频率分布为41.5%,A1298C位点C等位基因频率为20.8%,MTRR基因A66G位点G等位基因频率为27.5%。两组人群相比,MTHFR基因C677T,A1298C和MTRR基因A66G位点基因多态性分布差异无统计学意义(P>0.05)。200名孕妇血浆Hcy平均水平为(5.09±1.72)μmol/L,不同基因型孕妇血浆Hcy水平差异无统计学意义(P>0.05)。与对照组相比(4.76±1.71)μmol/L,病例组(5.43±1.67)μmol/L血浆Hcy水平显著升高,且差异具有统计学意义(P<0.05)。Logistic回归分析显示,孕妇血浆Hcy水平每升高一个单位,不良孕产发生的风险增加0.27倍(OR=1.27,95%CI:1.07~1.52,P<0.05);同样以血浆Hcy水平中位数5.23μmol/L为界值,经Logistic回归分析显示,血浆Hcy水平较高的孕妇不良孕产发生风险是Hcy水平较低孕妇的1.25倍(OR=2.25,95%CI:1.28~3.96,P<0.05)。结论荆州地区孕妇Hcy代谢相关酶基因MTHFRC677T、A1298C和MTRRA66G位点基因多态性与不良孕产史无明显关联,但血浆Hcy水平升高是不良妊娠发生的重要危险因素。

Objective To investigate the relationship between methylenetetrahydrofolate reductase(MTHFR),methionine synthase reductase methionine synthase reductase(MTRR)gene polymorphism and plasma homocysteine(Hcy).Methods A casecontrol study,including 100 participants with adverse pregnancy history and 100 participants without adverse pregnancy history,was conducted in Jingzhou Maternal and Child Health Care Hospital.Taqman-MGB was used to detect the genotypes of MTHFRC677T,A1298C,and MTRRA66G in oral mucosal epithelial cells.Enzymatic cycling assay was used to determine Hcy levels in plasma.Results Among 200 pregnant women,the frequency of the T allele of MTHFR C677T was 41.5%.The frequency of C allele of MTHFR A1298C was 20.8%.The frequency of A allele of MTRR A66G was 27.5%.There was no statistically significant difference in the frequencies of genotypes of MTHFR C677T,A1298C and MTRR A66G between the two groups(P>0.05).The average plasma Hcy level of 200 pregnant women was 5.09±1.72μmol/L.There was no significant difference in plasma Hcy levels among pregnant women with different genotypes(P>0.05).However,the plasma Hcy of the case group(5.43±1.67μmol/L)was significantly higher than that of the control group(4.76±1.71μmol/L).Logistic regression analysis showed that for every unit increasement of plasma Hcy,the risk of adverse maternal birth increased by 0.27 times(OR=1.27,95%CI:1.07,1.52,P<0.05).When the median plasma Hcy(5.23μmol/L)was used as the cut-off value,pregnant women with higher plasma Hcy levels experienced 1.25 times of risk of adverse pregnancy than pregnant women with lower Hcy levels(OR=2.25,95%CI:1.28,3.96,P<0.05).Conclusions There is no relationship between genetic polymorphisms of Hcy metabolism related enzyme genes(MTHFR C677T,A1298C and MTRR A66G)and adverse pregnancy history of pregnant women in Jingzhou.However,elevated plasma Hcy is a risk factor of adverse pregnancy outcomes.