MTHFR基因C677T多态性与妊娠期糖尿病患者血清维生素A、维生素E及妊娠结局的相关性分析

Correlation analysis of MTHFR C677T polymorphism with serum vitamin A,vitamin E and pregnancy outcome in patients with gestational diabetes mellitus

目的探讨MTHFR基因C677T多态性与妊娠期糖尿病患者血清维生素A、维生素E及妊娠结局的相关性分析。方法收集2016年1月至2020年6月在我院就诊的妊娠期糖尿病(gestational diabetes mellitus,GDM)患者100例,同期收集来我院分娩的正常孕妇100例作为对照组。通过提取两组研究对象的外周血DNA,经PCR扩增和Sanger测序鉴定亚甲基四氢叶酸还原酶(MTHFR)C677T基因多态性,包括野生型CC(CC型)和突变型CT(杂合型,即CT型)、TT(纯合型,即TT型)三种。采用酶联免疫吸附实验检测两组研究对象的血清维生素A和维生素E水平,观察两组研究对象的妊娠结局,分析MTHFR基因C677T多态性与妊娠期糖尿病患者血清维生素A、维生素E及妊娠结局的相关性。结果妊娠期糖尿病患者MTHFR基因C677T位点CC野生型占比和等位基因C频率均低于对照组(P<0.05),而TT纯合型占比和等位基因T频率高于对照组(P<0.05)。针对MTHFR基因C677T位点的妊娠期糖尿病发病风险进行比较,CC野生型的发病优势比0.650(P=0.039),而TT纯合型的发病优势比高达1.706(P<0.001)。单独比较突变型等位基因C和T频率,其优势比分别为0.789(P=0.045)、1.338(P=0.025)。妊娠期糖尿病患者孕早期、孕中期、孕晚期的血清维生素A和维生素E水平均明显低于正常对照组,早产、宫缩乏力、新生儿窒息、胎儿宫内窘迫、产后出血等不良妊娠结局发生率均明显高于正常对照组(P<0.05)。进一步针对MTHFR基因C677T多态性进行分析,妊娠期糖尿病患者CC组早期、孕中期、孕晚期的血清维生素A和维生素E水平最高,早产、宫缩乏力、新生儿窒息、胎儿宫内窘迫、产后出血等不良妊娠结局发生率最低,CT组次之、TT组最次(P<0.05)。但在正常妊娠孕妇CC组、CT组和TT组中,血清维生素A、维生素E水平和不良妊娠结局发生率均相近(P>0.05)。结论MTHFR基因C677T多态性与妊娠期糖尿病患者血清维生素A、维生素E及妊娠结局均存在密切的相关性,提示该位点的突变可能参与妊娠期糖尿病的发生和发展。

Objective:To investigate the correlation between MTHFR C677T polymorphism and serum vitamin A,vitamin E and pregnancy outcome in patients with gestational diabetes mellitus.Methods:100 cases of gestational diabetes mellitus(GDM)in our hospital were collected from January 2016 to June 2020,and 100 cases of normal pregnant women were collected as control group.The MTHFR C677T gene polymorphism was identified by PCR amplification and specific enzyme digestion,including wild-type CC(CC type),mutant CT(heterozygous type)and TT(homozygous type,TT type).The levels of serum vitamin A and vitamin E were detected by enzyme-linked immunosorbent assay(ELISA).The pregnancy outcomes of the two groups were observed.The correlation between MTHFR C677T polymorphism and serum vitamin A,vitamin E and pregnancy outcome in patients with gestational diabetes mellitus was analyzed.Results:The percentages of CC wild type and allele C frequency of MTHFR C677T locus in gestational diabetes mellitus patients were lower than those in the control group(P<0.05),while the proportion of TT homozygous type and allele t frequency in gestational diabetes mellitus patients were higher than those in the control group(P<0.05).Compared with the risk of gestational diabetes mellitus at C677T locus of MTHFR gene,the odds ratio of CC in wild type was 0.650(P=0.039),while that of TT homozygote was 1.706(P<0.001).The odds ratios of allele C and T were 0.789(P=0.045)and 1.338(P=0.025)respectively.The levels of serum vitamin A and vitamin E in patients with gestational diabetes mellitus in the early,middle and late pregnancy were significantly lower than those in the normal control group.The incidence of adverse pregnancy outcomes such as premature delivery,uterine atony,neonatal asphyxia,fetal distress,postpartum hemorrhage and other adverse pregnancy outcomes were significantly higher than those in the normal control group(P<0.05).Further analysis of MTHFR gene C677T polymorphism showed that the serum vitamin A and vitamin E were the highest in the CC group in the early,middle and late pregnancy,and the incidence of adverse pregnancy outcomes such as premature delivery,uterine inertia,neonatal asphyxia,fetal distress and postpartum hemorrhage was the lowest,followed by CT group and TT group(P<0.05).However,the levels of serum vitamin A and vitamin E and the incidence of adverse pregnancy outcomes were similar in CC group,CT group and TT group of normal pregnant women(P>0.05).Conclusion:MTHFR C677T polymorphism is closely related to serum vitamin A,vitamin E and pregnancy outcome in patients with gestational diabetes mellitus,suggesting that the mutation of MTHFR gene may be involved in the occurrence and development of gestational diabetes mellitus.