摘要目的 探讨5,10-亚甲基四氢叶酸还原酶(MTHFR)基因C677T多态性及其与孕期叶酸摄入水平交互作用与先天性心脏病(简称先心病)的关系.方法 限制相应条件收集104例先心病患者与208例对照,对其母亲孕期膳食摄入频率及相关因素进行调查;通过聚合酶链反应-限制性片段长度多态性(polymerase chain reaction restricted fragment length polymorphism,PCR-RFLP)并酶切检测儿童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104例中叶酸摄入不足的38例(占36.54%),对照组208例中叶酸摄入不足的21例(占10.10%),叶酸摄入减少与先心病发病增多有正相关关系(X2=31.614,v=1,P<0.0001),其OR值为1.417(95%CI:1.216～1.651),叶酸摄入水平低是子代先心病的危险因素;病例组104例中MTHFR基因的TT、CT、CC三种基因型分别为46例、42例和16例,对照组208例中相应的基因型分别为39例、114例和55例,病例组和对照组该基因型分布的差异有统计学意义(X2=23.13,v=2,P<0.0001),MTHFR 677TT基因型是先心病的易感因素,OR值为3.437倍(95%CI:2.042～5.784).孕期叶酸摄入水平低与MTHFR 677TT基因型之间对先心病发生具有正相加交互作用,调整父母年龄、胎龄、性别等因素前后,交互作用的效应量分别为13.343、15.911,归因交互效应百分比分别为0.619和0.612,纯因子间归因交互效应百分比分别为0.649和0.637,根据估计的人群暴露率计算的一般人群预防分值为25.26%和27.82%.结论 孕期叶酸摄入水平低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基因型;MTHFR 677TT基因型与叶酸摄入水平低具有协同作用,在MTHFR 677 TT高危个体中,有效提高孕期叶酸摄入水平,可使人群先心病的发生下降,可对先心病的临床早期诊断和群体预防提供依据.

abstractsObjective To investigate the correlationship between congenital heart disease and 5,10-methylenetetra hydrofolate reductase (MTHFR)'s C677T or folacin intakes, and to study the interaction of them in the occurring of congenital heart disease. Methods We used case-control study (case=104, control=208) method. Cases and controls were chosen by age,sex and other conditions. The MTHFR C677T genotype distribution was analyzed by using polymerase chain reaction restricted fragment length polymorphism (PCR-RFLP) ,and non-conditional and multi-conditional logistic regression analysis were also used to analyze the correlationship and interaction of the factors. Results In case group, the number of people in low folacin intake level was 38(36. 54%) ,which in control group was 21 (10.10%). The intake level of folacin during pregnancy was related to congenital heart disease (X2=31.614, v=1, P<0.0001). The value of OR was 1. 417 with 95%CI 1.216-1.651 ,indicating that the low level of folacin intakes was a risk factor to the congenital heart disease. In case group,the number of TT genotype was 46 (44.24%) ,the number of CT genotype was 42 (40.38%) ,the number of CC genotype was 16(15.38%). In control group, the number of TT genotype was 39 (18.75%) ,the number of CT genotype was 114 (54.81%) ,the number of CC genotype was 55 (26.44%). A significant genotype distribution difference was identified between case and control group (X2=23.13, v=2, P<0.0001). Genotype MTHFR 677TF was a risk factor of congenital heart disease and the OR value was 3.437 (95% CI:2.042-5.784). The interaction analysis suggested that the low level of folacin intakes and the MTHFR 677TF genotype had a positive adding effect in the occurring of congenital heart disease. After adjusted some factors such as the ages of parents, fetus age and sex, the effect values of interaction were 13.343 and 15.911 respectively, and the percentages of attributable interaction effects were 0. 619 and 0. 612. The percentages of effect values of interaction between pure factors were 0. 649 and 0. 637 and the population attributable risks were 25.26% and 27. 82% according to the estimated exposure rate of population risk factors. Conclusion The low level of folacin intakes during pregancy should be a risk factor to congenital heart disease and the MTHFR 677TT genotype be correlated to congenital heart disease. There is interaction between folacin intakes and the MTHFR 677TT genotype. Increasing the intakes of folacin among MTHFR 677TT genotype people might decrease the incidence rate of congenital heart disease.