孕期生活事件及亚甲基四氢叶酸还原酶基因多态性与子代先天性心脏病的关联

目的探讨孕期应激性生活事件、亚甲基四氢叶酸还原酶(MTHFR)基因C677T多态性及其交互作用与子代先天性心脏病的关系。方法采用以医院为基础的病例对照研究设计,按照纳入和剔除标准选择144例病例与168例对照,对母亲进行问卷调查,收集人口统计学信息、孕期健康状况、孕期生活事件;并收集静脉血,通过聚合酶链反应—限制性片段长度多态性(polymerase chain reaction restricted fragmentlength polymorphism,PCR-RFLP)检测MTHFR C677T基因型。采用单因素和多因素非条件logistic回归模型,进行影响因素关联强度及交互作用分析。结果病例组和对照组一般情况指标差异无统计学意义。应激性生活事件阳性与子代先心病发生有关联,其OR值分别为2.248(95%CI:1.139～4.433),调整混杂因素后,OR值为2.851(95%CI:1.624～4.981)。两组MTHFR 677TT基因型频率和T等位基因频率的差异有统计学意义(χ2=22.38,P<0.001;χ2=20.36,P<0.000 1),MTHFR 677TT基因型与先心病风险的OR为3.215(95%CI:1.958～5.280);MTHFR 677TT基因型与应激性生活事件阳性之间具有正相加交互作用,调整混杂因素前后,TT基因型与应激性生活事件阳性的I(AB)为6.521、7.324,AP(AB)为35.5%、42.2%,AP*(AB)为40.8%、52.4%。结论孕期应激性生活事件阳性是子代先心病发生的危险因素;MTHFR 677TT基因型是先心病的易感因素;MTHFR 677TT基因型与孕期应激性生活事件对先心病具有协同作用。

Studies on correlations between congenital heart disease and MTHFR C677T polymorphism or unexpected stressful life events during pregnancy

Objective To investigate the correlation between congenital heart disease(CHD) and 5,10-methylenetetra hydrofolate reductase(MTHFR) C677T polymorphism or maternal exposure to unexpected stressful life events during pregnancy and to find out how these events interact with MTHFR gene in the occurring of CHD.Methods A case-control study was conducted with a total of 144 cases and 168 controls selected according to strict criteria,and all the mothers of subjects were required to complete a questionnaire including Life Events Checklist before delivery.Blood samples were collected and MTHFR C677T genotype was identified by polymerase chain reaction restricted fragment length polymorphism(PCR-RFLP).The correlation and interaction were analyzed using single and multiple unconditional logistic regression models.Results The occurrence of CHD was associated with the exposure of stressful life events during pregnancy(OR:2.248,95%CI:1.139-4.433) and after adjusting the confounding factors,the odds ratio changed to 2.851(95%CI:1.624-4.981).Also the study showed that the frequency of MTHFR C677TT genotype and T allele were both higher in case group than that in control(χ2=22.38,P<0.001;χ2=20.36,P<0.0001).Meanwhile the correlation between MTHFR C677TT genotype and CHD risk was quite positive(OR: 3.215,95%CI:1.958-5.280).The interaction analysis suggested that exposure to stressful life events and the MTHFR 677TT genotype interacted positively with each other to increase the risks of CHD.After adjusting the confounding factors,the I(AB) of TT genotype and exposure to stressful life events were 6.521and 7.324 with AP(AB) of 35.5% and 42.2%,as well as AP*(AB) of 40.8 % and 52.4%.Conclusions The MTHFR 677TT genotype is one of the risk factors of congenital heart disease and exposure to stressful life events during pregnancy is also attributable to the formation of heart defects.These two events can interact with each other to enhance the risks of CHD.