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CYP450基因多態(tài)性及環(huán)境危險(xiǎn)因素暴露與先天性心臟病關(guān)系病例對照研究

發(fā)布時間:2018-03-01 11:20

  本文關(guān)鍵詞: 先天性心臟病(CHD) CYP基因多態(tài)性 環(huán)境危險(xiǎn)因素暴露 交互作用 出處:《中國公共衛(wèi)生》2017年09期  論文類型:期刊論文


【摘要】:目的探討子代CYP450基因多態(tài)性及母親孕期環(huán)境危險(xiǎn)因素暴露與先天性心臟病(CHD)發(fā)病的關(guān)系以及二者在CHD發(fā)生中是否存在交互作用。方法采用病例對照研究方法,將2011年10月-2013年1月在山東省濟(jì)寧醫(yī)學(xué)院第一附屬醫(yī)院確診的160例0~7周歲單純性CHD患兒和同期在該院進(jìn)行體檢或就診的160例非心臟病幼兒分別作為病例組和對照組,采用訪談方式進(jìn)行問卷調(diào)查,獲得研究對象母親孕期環(huán)境危險(xiǎn)因素暴露信息,采集研究對象空腹靜脈,血應(yīng)用聚合酶鏈反應(yīng)-限制性片段長度多態(tài)性分析法(PCR-RFLP)檢測CYP450基因多態(tài)性;應(yīng)用單因素和多因素條件logistic回歸模型分析子代CYP450基因多態(tài)性和母親孕期環(huán)境危險(xiǎn)因素暴露與CHD發(fā)病的關(guān)聯(lián)強(qiáng)度,并采用相加模型交互作用指標(biāo)評價(jià)二者的交互作用。結(jié)果多因素條件logistic回歸分析結(jié)果顯示,子代CYP1A1基因rs1048943位點(diǎn)純合子突變型是CHD發(fā)病的保護(hù)因素(OR=0.369,95%CI=0.138~0.986);母親孕前3個月使用染發(fā)劑(OR=5.621.95%CI=1.401~22.541)、孕前3個月被動吸煙(OR=2.511,95%CI=1.342~4.699)、孕早期被動吸煙(OR=2.441,95%CI=1.306~4.561)、孕早期居住在3年內(nèi)裝修過的居室(OR=4.159,95%CI=1.698~10.182)和孕早期服用解熱鎮(zhèn)痛藥(OR=3.901,95%CI=1.271~11.971)是CHD發(fā)病的危險(xiǎn)因素。交互作用分析結(jié)果顯示,子代攜帶CYPIA1 rs1048943位點(diǎn)純合子突變型有減弱環(huán)境因素致病風(fēng)險(xiǎn)的趨勢,但交互作用指標(biāo)無統(tǒng)計(jì)學(xué)意義。結(jié)論子代攜帶CYP1A1純合子突變型對CHD發(fā)病有保護(hù)作用,母親孕前及孕早期應(yīng)盡量避免或減少環(huán)境危險(xiǎn)因素的暴露,以預(yù)防子代CHD的發(fā)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.
【作者單位】: 復(fù)旦大學(xué)公共衛(wèi)生學(xué)院;上海市計(jì)劃生育科學(xué)研究所;濟(jì)寧醫(yī)學(xué)院公共衛(wèi)生學(xué)院;天津醫(yī)科大學(xué)公共衛(wèi)生學(xué)院;
【基金】:上海市出生缺陷重點(diǎn)實(shí)驗(yàn)室2015年開放課題(15DZKF1009)
【分類號】:R725.4

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