CYP450基因多态性及环境危险因素暴露与先天性心脏病关系病例对照研究

目的 探讨子代CYP450基因多态性及母亲孕期环境危险因素暴露与先天性心脏病（CHD）发病的关系以及二者在CHD发生中是否存在交互作用。方法 采用病例对照研究方法，将2011年10月-2013年1月在山东省济宁医学院第一附属医院确诊的160例0~7周岁单纯性CHD患儿和同期在该院进行体检或就诊的160例非心脏病幼儿分别作为病例组和对照组，采用访谈方式进行问卷调查，获得研究对象母亲孕期环境危险因素暴露信息，采集研究对象空腹静脉，血应用聚合酶链反应-限制性片段长度多态性分析法（PCR-RFLP）检测CYP450基因多态性；应用单因素和多因素条件logistic回归模型分析子代CYP450基因多态性和母亲孕期环境危险因素暴露与CHD发病的关联强度，并采用相加模型交互作用指标评价二者的交互作用。结果 多因素条件logistic回归分析结果显示，子代CYP1A1基因rs1048943位点纯合子突变型是CHD发病的保护因素（OR=0.369，95%CI=0.138~0.986）；母亲孕前3个月使用染发剂（OR=5.621，95%CI=1.401~22.541）、孕前3个月被动吸烟（OR=2.511，95%CI=1.342~4.699）、孕早期被动吸烟（OR=2.441，95%CI=1.306~4.561）、孕早期居住在3年内装修过的居室（OR=4.159，95%CI=1.698~10.182）和孕早期服用解热镇痛药（OR=3.901，95%CI=1.271~11.971）是CHD发病的危险因素。交互作用分析结果显示，子代携带CYP1A1 rs1048943位点纯合子突变型有减弱环境因素致病风险的趋势，但交互作用指标无统计学意义。结论 子代携带CYP1A1纯合子突变型对CHD发病有保护作用，母亲孕前及孕早期应尽量避免或减少环境危险因素的暴露，以预防子代CHD的发生。

Associations of CYP450 gene polymorphism and exposed to environmental risk factors with congenital heart disease:a case-control study

Objective To explore the effects of maternal environmental risk factor exposure and gene polymorphisms of cytochrome P450 (CYP450) on congenital heart disease (CHD) in infants,and to assess whether there is an interactive effect between maternal environmental risk factors and gene polymorphisms of CYP450 on CHD.Methods A hospital-based matched case-control study (1:1) was conducted from October 2011 to January 2013.A total of 160 children of 0-7 years old with isolated CHD (cases) and 160 children without any congenital malformations (controls) were recruited.Mothers of the cases and controls were interviewed to obtain information on demographic characteristics of the mother-baby pairs,as well as maternal toxicants exposures during the first trimester of pregnancy.The genotype of CYP450 was determined with polymerase chain reaction restricted fragment length polymorphism (PCR-RFLP).Univariate and multivariate logistic regression were used to assess the association between maternal environmental exposure and gene polymorphisms of CYP450 and the risk of CHD in their infants.Three indexes were used to evaluate the biological interactions between the CYP1A1 homozygous mutant type and CHD.Results The results of multivariate conditional logistic regression demonstrated that the offspring's homozygous mutant type of CYP1A1 rs1048943 was a protective factor for CHD (odds ratio[OR]=0.369,95% confidence interval[CI]:0.138-0.986).Maternal usage of hair dyeing during 3 months before the pregnancy (adjusted odds ratio[aOR]=5.62,95%CI:1.401-22.541),exposed to passive smoking during 3 months before the pregnancy (aOR=2.511;95%CI:1.342-4.699) and during the first trimester (aOR=2.441,95%CI:1.306-4.561),living in a house decorated within past 3 years during the first trimester (aOR=4.159,95%CI:1.698-10.182),and taking analgesic or antipyretic drug during the first trimester (aOR=3.901,95%CI=1.271-11.971) were associated with an increased risk of CHD.The effects of environmental factors mentioned above on CHD could be attenuated when the infants carrying homozygous mutant type of CYP1A1 rs1048943,but the interactive effect indexes were of no statistical significance.Conclusion Carrying homozygous mutant type of CYP1A1 plays a protective role on the occurrence of CHD for offsprings.Avoiding or reducing maternal exposure to environmental risk factors before the pregnancy and during the first trimester might help to prevent the offspring from congenital heart disease.