Tao Jing, Li Nana, Liu Zhen, Deng Ying, Li Xiaohong, Chen Ming, Yu Jing, Zhu Jun, Yu Ping, Wang Yanping
National Center for Birth Defect Monitoring, West China Second University Hospital, Sichuan University.
Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, Sichuan.
Medicine (Baltimore). 2019 Jul;98(30):e16556. doi: 10.1097/MD.0000000000016556.
Polycyclic aromatic hydrocarbons (PAHs) may be 1 of etiologic factors responsible for congenital heart diseases (CHDs). Variations of the microsomal epoxide hydrolase (EPHX1) gene, as well as their possible interactions with PAHs exposure, may increase susceptibility to CHDs.This case-control study investigated the risk of CHDs in relation to the EPHX1 polymorphisms and assessed the interactions between these polymorphisms and PAHs exposure in 357 mothers of CHDs fetuses and 270 control mothers. Logistic regression models for the risk of CHDs were applied to determine the effect of genetic polymorphisms using additive, recessive, and dominant genetic models, as well as gene-exposure interactions. Multiple testing was adjusted by applying the false discovery rate (FDR).None of the maternal genetic polymorphisms of EPHX1 was associated with CHDs occurrence. Only the single nucleotide polymorphism rs1051740 was associated with an increased risk of right-sided obstructive malformations under the recessive model (adjusted odds ratio [aOR] = 1.852, 95% confidence interval [CI]: 1.065, 3.22) before FDR correction. A possible modifying effect of PAHs exposure on genetic polymorphisms of EPHX1 was found in susceptibility to CHDs, though no multiplicative-scale interactions between maternal exposure to PAHs and polymorphisms of EPHX1 gene were seento affect the risk of CHDs.The role of EPHX1 gene polymorphisms for CHDs need to be further evaluated, in particularly by interacting with PAHs exposure.
多环芳烃（PAHs）可能是先天性心脏病（CHDs）的病因之一。微粒体环氧化物水解酶（EPHX1）基因的变异及其与PAHs暴露的可能相互作用，可能会增加患CHDs的易感性。本病例对照研究调查了357名CHDs胎儿的母亲和270名对照母亲中CHDs与EPHX1基因多态性的关系，并评估了这些多态性与PAHs暴露之间的相互作用。应用CHDs风险的逻辑回归模型，使用加性、隐性和显性遗传模型以及基因-暴露相互作用来确定基因多态性的影响。通过应用错误发现率（FDR）对多重检验进行校正。EPHX1的母体基因多态性均与CHDs的发生无关。在FDR校正前，仅单核苷酸多态性rs1051740在隐性模型下与右侧阻塞性畸形风险增加相关（校正比值比[aOR]=1.852，95%置信区间[CI]：1.065，3.22）。虽然未发现母体PAHs暴露与EPHX1基因多态性之间存在乘法尺度相互作用影响CHDs风险，但发现PAHs暴露对EPHX1基因多态性在CHDs易感性方面可能具有修饰作用。EPHX1基因多态性在CHDs中的作用需要进一步评估，特别是通过与PAHs暴露相互作用来评估。
