孕母叶酸摄入与MTHFR基因C677T多态性对子代先天性心脏病发病风险研究

Effects of Periconceptional Folate Intake and Methylenetetrahydrofolate Reduetase Gene C667T Polymorphism of Pregnant Women on Congenital Heart Diseases in Offspring

目的分析孕母孕早期环境高危因素,探讨叶酸摄入与MTHFR基因多态性间交互作用对子代先天性心脏病(简称先心病)发病的影响。方法通过病例对照研究回顾性分析98例12岁以下先心病患者母亲和101例正常婴儿的母亲(对照组)孕期危险因素暴露水平以及叶酸摄入情况,进一步应用变性液相高效色谱(DHPLC)检测MTHFR基因C677T多态性,并分析其与叶酸摄入的交互作用。结果经Logistic回归分析,6项因素纳入先心病风险模型,孕母教育程度、没有定期产检、精神紧张、接触化学物质是子代先心病的高危因素,服用叶酸和复合维生素是先心病的保护因素。叶酸补充充足情况下,MTHFR基因各基因型比较,病例组与对照组无统计学差异。将间断服用及未服用叶酸者合并作为叶酸补充不足者,其孕母基因型为CT与CC时发病无统计学意义(P=0.066,OR=2.018,95%CI:0.95～4.285)。结论提高孕母的自我保健意识是减少先心病危险因素暴露的重要措施。怀孕早期孕母叶酸的补充不足可能是导致子代先心病发病风险增高的独立因素,孕母MTHFR基因C677T基因型合并叶酸补充不足可能增加先心病风险。

Objective To explore the environmental risk factors, periconceptional folate intake and methylenetetrahydrofolate reduetase （MTHFR） gene C667T polymorphism of pregnant women on congenital heart diseases （CHD） in offspring. Methods Retrospective ease-control study was carried out to investigate periconeeptional folate supplementation and environmental factors in 98 parents with CHD offsprings and 101 parents with normal offsprings. The mothers＇ MTHFR gene C667T mutation was also identified. The possible risk factors were analyzed by simple and multiple factors Logistic regression methods. Results Six factors were related to the occurrence of CHD in the offspring： education of gestation mother, no prenatal examination, under depressed or nervous condition during pregnancy and maternal exposures to harmful substance; periconceptional folate and compound vitamin supplementation were protection factors. There were significant difference between case and control group in folate supplement （P〈 0.05）. The maternal MTHFR 677genotypes CC and TT in combination with daily folate supplements were associated with no increased risk for CHD in offspring, however in combination with not use of folate a two-fold （P--0.066, OR= 2.018, 95%CI 0.95- 4.285）increased risk. Conclusion Improving self health care of gestational mother is the most important protection measures to avoid the risk factors exposure. Periconeeptional folate deficiency may be the independence risk factor for CHD. Perieoneeptional mother carrying MTHER heterozygote＇ s（CT） genotype in combination with deficiency may increase risk for CHD.