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首页> 外文期刊>Cardiovascular toxicology >A Functional Aryl Hydrocarbon Receptor Genetic Variant, Alone and in Combination with Parental Exposure, is a Risk Factor for Congenital Heart Disease
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A Functional Aryl Hydrocarbon Receptor Genetic Variant, Alone and in Combination with Parental Exposure, is a Risk Factor for Congenital Heart Disease

机译：单独和与父母暴露的功能性芳基烃受体遗传变异是先天性心脏病的危险因素

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Recent experimental studies showed that ablation of the aryl hydrocarbon receptor (AhR) as well as its activation by exogenous ligands disrupt the molecular networks involved in heart formation and function, leading to congenital heart disease (CHD). However, no evidence is available about the role of AhR in humans. We assessed the prevalence of a functional AhR genetic variant (p.Arg554Lys) in CHD patients as well as its joint effects with parental exposure. A total of 128 CHD patients (76 males; age 6.2 +/- 6.7 years) and 274 controls (160 males; age at birth) were genotyped for the AhR polymorphism by using the TaqMan(A (R)) Drug Metabolism Genotyping assay. Both case and control parents completed a structured questionnaire on demographic, lifestyle and preconception exposures. Genotype (p = 0.001) and allele (p 0.0001) distributions of AhR p.Arg554Lys differed significantly between patients and controls. A significant elevated CHD risk was found under dominant (OR = 2.9, 95% CI 1.9-4.6, p 0.0001) and additive genetic models (OR = 6.2, 95% CI 2-19, p = 0.001). There was a significant interaction between 554-Lys allele and paternal smoking exposure (ORsmoking = 1.6, 95% CI = 0.9-2.9; ORallele = 2.6, 95% CI = 1.3-5; ORinteraction = 4.9, 95% CI = 2.4-9.9, p (interaction) 0.0001). Additionally, 554-Lys allele exacerbated the effect of maternal periconceptional exposure (ORexposure = 1.6, 95% CI = 0.8-3; ORallele = 2.6, 95% CI = 1.5-4.5; ORinteraction = 5.7; 95% CI = 2.6-12, p (interaction) 0.0001). Our findings showed that the AhR p.Arg554Lys polymorphism, alone and in combination with parental exposures, is associated with the CHD risk, highlighting the significant role of AhR in the cardiovascular development.
机译：最近的实验研究表明，芳基烃受体（AHR）的消融以及外源配体的激活破坏了心脏形成和功能的分子网络，导致先天性心脏病（CHD）。但是，没有证据表明AHR在人类中的作用。我们评估了CHD患者中功能性AHR遗传变异（P.ARG554LY）的患病率，以及与父母暴露的关节效应。共有128名CHD患者（76名男性; 6.2岁+/- 6.7岁）和274名对照（160名男性;出生时的年龄）是通过使用Taqman（A（R））药代谢基因分型测定的AHR多态性的基因分型。两种案例和控制父母都在人口统计学，生活方式和先入为主暴露方面完成了结构化问卷。基因型（P = 0.001）和等位基因（P＆LT; 0.0001）AHR P.ARG554的分布在患者和对照之间有显着不同。在占优势（或= 2.9,95％CI 1.9-4.6，P <0.0001）和添加遗传模型（或= 6.2,95％CI 2-19，P = 0.001）下发现显着升高的CHD风险。 554-lys等位基因和父毒吸烟暴露之间存在显着的相互作用（Orsmoking = 1.6,95％Ci = 0.9-2.9; Orlalle = 2.6,95％Ci = 1.3-5; Orinteraction = 4.9,95％Ci = 2.4-9.9 ，p（相互作用）＆ 0.0001）。此外，554-Lys等位基因加剧了母体仔细暴露的效果（Orposences = 1.6,95％Ci = 0.8-3; Orlalle = 2.6,95％Ci = 1.5-4.5; Orinteraction = 5.7; 95％Ci = 2.6-12， P（相互作用）＆ 0.0001）。我们的研究结果表明，AHR P.ARG554LYS多态性，单独和与父母暴露组合，与CHD风险相关，突出了AHR在心血管发展中的显着作用。

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