基于MTHFR基因多态性分析不同时期叶酸摄入与子痫前期及其亚型的相关性

目的基于亚甲基四氢叶酸还原酶(MTHFR)基因多态性分析不同时期叶酸(FA)摄入与子痫前期及亚型的相关性。方法选取2017年6月-2018年12月在该院进行治疗的180例子痫前期孕妇为研究组,根据不同子痫前期亚型将研究组分为轻度子痫前期组98例和重度子痫前期组82例;另选取同期该院收治的50例健康孕妇为对照组。比较各组孕妇血清中同型半胱氨酸(Hcy)、FA及维生素B12(VitB12)含量,测定各组孕妇外周血中MTHFR基因多态性,比较不同基因型中Hcy、FA及VitB12水平,并将各指标间及指标水平与病情程度进行相关性分析,同时观察各组孕妇妊娠结局。结果子痫前期孕妇血清中Hcy水平明显高于对照组,FA水平明显低于对照组,差异均有统计学意义(均P<0.05)。轻度子痫前期孕妇血清中VitB12水平明显低于对照组及重度子痫前期组,差异均有统计学意义(均P<0.05)。子痫前期孕妇MTHFR基因C677T位点中CC及CT基因型比例明显低于对照组,子痫前期孕妇MTHFR基因C677T位点中TT基因型比例明显高于对照组;子痫前期孕妇T等位基因频率明显高于对照组,C等位基因频率明显低于对照组;TT及CT基因型孕妇血清中Hcy水平明显高于CC基因型孕妇,TT及CT基因型孕妇血清中FA及VitB12水平明显低于CC基因型孕妇,差异均有统计学意义(均P<0.05)。子痫前期孕妇血清中Hcy水平与FA呈负相关关系(P<0.05);子痫前期孕妇血清中FA水平与VitB12呈正相关关系(P<0.05);血清中Hcy水与子痫前期孕妇病情程度呈正相关关系(P<0.05);血清中FA水平与子痫前期孕妇病情程度呈负相关关系(P<0.05)。重度子痫前期孕妇胎盘早剥、剖宫产、早产、低体质量儿、胎儿窘迫、新生儿窒息及死胎的发生率明显高于轻度子痫前期组及对照组,差异均有统计学意义(均P<0.05)。结论MTHFR基因C677T位点可通过影响体内Hcy、FA及VitB12水平参与子痫前期过程,同时FA的缺乏可导致体内Hcy水平升高,可能是导致子痫前期发生重要原因,MTHFR基因多态性可作为预测子痫前期孕妇妊娠结局的风险指标。

Correlation between folic acid intake and preeclampsia and its subtypes in different periods based on MTHFR gene polymorphism

Objective To discuss the correlation between folic acid(FA)intakeand preeclampsia and its subtypes in different periods based on MTHFR gene polymorphism.Methods Selected 180 cases of preeclampsia pregnant women who were treated in the hospital from June 2017 to December 2018 as the study group.The study group was divided into mild preeclampsia group(98 cases)and severe preeclampsia group(82 cases)according to different preeclampsia subtypes.In addition,50 healthy pregnant women who were treated in the hospital in the same period were selected as the control group.The levels of homocysteine(Hcy),FA and vitamin B12(VitB12)in the serum of pregnant women in each group were compared.And the MTHFR gene polymorphism in peripheral blood of pregnant women in each group were measured.Further,the Hcy,FA and VitB12 levels in different genotypes were compared and the correlation between indexes or each index and the degree of pathogenetic condition was analyzed.Meanwhile,the pregnancy outcome of pregnant women in each group was observed.Results In preeclampsia pregnant women,serum Hcy level was significantly higher than that of the control group,and the FA level was markedly lower than that of the control group,all with statistically significant differences(all P<0.05).Serum VitB12 level in mild preeclampsia group was distinctly lower than that of the control group and severe preeclampsia group,the differences of which were statistically significant(all P<0.05).In mild preeclampsia group,the proportions of CC and CT genotypes in C677T locus of MTHFR gene were obviously lower than that in the control group but the proportion of TT genotype was markedly higher than that of the control group;the frequency of T allele was significantly higher than that of the control group;the frequency of C allele was dramatically lower than that of the control group.Serum Hcy expression of TT genotype and CT genotype pregnant women was remarkably higher than that of CC genotype pregnant women,however,serum FA and VitB12 expression of TT genotype and CT genotype pregnant women was remarkably lower than that of CC genotype pregnant women,all with statistically significant differences(all P<0.05).Among preeclampsia pregnant women,serum Hcy expression was negatively related with FA expression(P<0.05);serum FA expression was positively related with VitB12 expression(P<0.05);serum Hcy expression was in positive association(P<0.05)and FA expression was in negative association with the degree of pathogenetic condition(P<0.05).The incidence rates of placental abruption,cesarean section,premature delivery,low-birth-weight infants,fetal distress,neonatal asphyxia and stillbirth in severe preeclampsia group was significantly higher than those in mild preeclampsia group and control group,with all differences statistically significant(all P<0.05).Conclusion The C677T locus of MTHFR gene could participate in the process of preeclampsia by influencing Hcy,FA and VitB12 levels.The lack of FA resulted in the elevation of Hcy expression,which might be the main reason for the occurrence of preeclampsia.MTHFR gene polymorphism can be used as a predictor for the pregnancy outcomes of preeclampsia pregnant women.