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
本文关键词: 先天性心脏病(CHD) CYP基因多态性 环境危险因素暴露 交互作用 出处:《中国公共卫生》2017年09期 论文类型:期刊论文
【摘要】: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CYPIA1 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。
[Abstract]:Objective to investigate the relationship between maternal exposure to maternal environmental risk factors and the incidence of congenital heart disease (CHD) and whether there is interaction between the polymorphism of CYP450 gene and maternal risk factors in the development of congenital heart disease. Methods Case-control study was used to study the relationship between the polymorphisms of CYP450 gene and the incidence of congenital heart disease. From October 2011 to January 2013, 160 children with simple CHD aged 0 to 7 years old diagnosed in the first affiliated Hospital of Jining Medical College of Shandong Province and 160 children with non-heart disease who were examined or visited in the same period were taken as the case group and the control group, respectively. Questionnaire survey was conducted to obtain the exposure information of maternal environmental risk factors during pregnancy, and the fasting veins of the subjects were collected. CYP450 gene polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP). Univariate and multivariate conditional logistic regression models were used to analyze the association between maternal exposure to maternal environmental risk factors and CYP450 gene polymorphisms. The interaction index of additive model was used to evaluate the interaction between the two. Results the results of multivariate conditional logistic regression analysis showed that, The homozygous mutation at rs1048943 locus of CYP1A1 gene in offspring is the protective factor of CHD. The mother uses hair dye OR5.621.95CII 1.401a 22.541 in 3 months before pregnancy, OR2.51195CI1.3424.699 in the first trimester of pregnancy, 2.44195CII 1.3066.561in the first trimester of pregnancy and 1.3066.561in the first trimester of pregnancy. The risk factors of CHD were 4.159 ~ 95% CIQ 1.698 + 10.182) and the antipyretic analgesics 3.901 ~ 95% ~ 1.271 ~ 11.971) in early pregnancy, and the results of interaction analysis showed that, The homozygous mutation of CYPIA1 rs1048943 locus in progeny had the tendency to reduce the risk of environmental factors, but there was no statistical significance in the index of interaction. Conclusion the homozygote mutation of CYP1A1 in offspring has protective effect on the pathogenesis of CHD. Mothers should avoid or reduce exposure to environmental risk factors before pregnancy and early pregnancy in order to prevent the occurrence of CHD in their offspring.
【作者单位】: 复旦大学公共卫生学院;上海市计划生育科学研究所;济宁医学院公共卫生学院;天津医科大学公共卫生学院;
【基金】:上海市出生缺陷重点实验室2015年开放课题(15DZKF1009)
【分类号】:R725.4
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