MTHFR基因多态性及环境因素与先天性心脏病关系

目的探讨5,10-亚甲基四氢叶酸还原酶(MTHFR)基因C677T基因位点突变与先天性心脏病(CHD)关系以及环境因素交互作用。方法采用病例-对照研究设计,以104例CHD患者与208例对照为研究对象,用聚合酶链反应-限制性片段长度多态性分析法检测MTHFR基因C677T变异,运用logistic回归相加模型计算MTHFR C677T基因TT型与部分环境因素交互作用。结果病例组MTHFR出现纯合(TT)频率为44.24%,对照组为18.75%,差异有统计学意义(χ²=22.71,P<0.01);T等位基因分布病例组为64.42%,对照组为46.15%,差异有统计学意义(χ²=18.55,P<0.01);多因素logistic回归分析表明,MTHFR基因677TT型是CHD易感基因,OR值为3.40(95%CI=1.63~7.11),7个环境危险因素分别为孕期妊高症、使用解热镇痛药、接触农药、膳食较差、蔬菜摄入较少、负性生活事件发生、父亲饮酒指数较高,环境危险因素与MTHFR基因677TT型交互作用人群归因危险度百分比(PAR%)为6.03%~27.20%。结论针对携带MTHFR 677位TT突变基因型高危个体,控制环境危险因素,可降低人群中CHD发生约6%~27%。

Associations of MTHFR gene polymorphism and environmental factors with congenital heart disease

ObjectiveTo investigate the association of 5,10-methylenetetrahydrofolate reductase(MTHFR)’s C677T genetic point mutation with congenital heart disease(CHD) and its interaction with environmental factors.MethodsWith case-control design,104 CHD cases and 208 controls were examined.The logistic regression model was used to assess MTHFR C677T genotype variation with polymerase chain reaction restricted fragment length polymorphism(PCR-RFLP).Indicators of quantitative analysis for interaction between MTHFR gene 677TT and some of environmental factors were calculated with stratified multiplicative logistic regression model.ResultsIn the case group,the change frequency of C to T of MTHFR gene’ C667T gene was 44.24%,while the frequency was 18.75% in the control group,with a significant difference between the two groups (P<0.01).In addition,the distribution of T allele was 64.42% in the case group while it was 46.15% in the control(P<0.01).Multiple factor logistic regression analyses(α=0.05) indicated that MTHFR 677TT genetype probably was a susceptible gene (odds ratio=3.40,95% confidence interval:1.63-7.11).Seven environmental risk factors for CHD identifed were gestational hypertension,antipyretic and analgesic usage,pesticide exposure,malnutrition,low intake of vegetales,negative life event,and excessive alcohol drinking of the father with the ORs of 29.78,16.90,10.95,2.23,5.47,6.62,and 2.23,respectively.The interaction regression model analyses for the seven environmental risk factors and MTHFR 677TT genetype showed that the population attributable risks for CHD were 9.89,6.03,11.00,17.52,27.20,9.17,and 17.71,respectively.ConclusionFor patients with MTHFR 677TT genetype,the CHD incidence could be reduced by 6%-27% if seven risk factors are controlled effectively.