Abstract
The major causes of congenital heart diseases (CHDs) are the interactions of genetic and environmental factors. We conducted a case–control study in 357 mothers of CHDs fetuses and 270 control mothers to investigate the association of maternal PAHs exposure, AHR, CYP1A1, CYP1A2, CYP1B1 and CYP2E polymorphisms, the interaction between PAHs exposure and genetic variants with the risk of CHDs. The higher level PAHs exposure was associated with the risk of CHDs (aOR = 2.029, 95% CI: 1.266, 3.251) or subtypes. The haplotypes of AHR or CYP1A2 were associated with the risk of CHDs: AHR: C-G-A-C: aOR = 0.765; T-A-G-A: aOR = 1.33; CYP1A2: A-T:aOR = 1.75; C-C: aOR = 0.706. When exposed to higher level PAHs, the risk of CHDs among the mothers carrying rs2158041 “C/T or T/T” genotype or rs7811989 “G/A or A/A” genotype in AHR was 1.724 (χ2 = 7.209, P = 0.007) or 1.735 (χ2 = 7.364, P = 0.007) times greater than the aOR in the mothers carrying wild genotype. The multiplicative-scale interactions between PAHs exposure and polymorphisms of CYP1A2 rs4646425 (P = 0.03) or CYP2E1 rs915908 (P = 0.0238) on the risk of CHDs were observed. Our study suggests that maternal AHR polymorphisms may modify the association of PAHs exposure with CHDs, CYP1A2 or CYP2E1 polymorphisms significantly interact with PAHs exposure on CHDs.
Highlights
Congenital heart diseases (CHDs) are the most common type of birth defect, accounting for one-third of all major congenital anomalies[1]
Significant positive associations were observed between maternal exposure to Polycyclic aromatic hydrocarbons (PAHs) and various congenital heart diseases (CHDs) phenotypes when comparing high exposure to low exposure after adjusting for potential confounders: all CHDs, septal defects, conotruncal heart defects, right-sided obstructive malformations, left-sided obstructive malformations, anomalous pulmonary venous return, and other heart abnormalities
No multiplicative-scale interactions were observed between maternal exposure to PAHs or the other SNPs and the risk of CHDs. In this case-control study, we evaluated the association between maternal exposure to PAHs and the risk of CHDs and the association between maternal genetic variants and the risk of CHDs
Summary
Congenital heart diseases (CHDs) are the most common type of birth defect, accounting for one-third of all major congenital anomalies[1]. Advances in the understanding of the genetic risk factors and environmental risk factors affecting the development of CHDs have been made, the aetiology of the majority of CHDs remains unknown[5,6,7]. Owing to the limitation of using expert industrial hygienists’ assessments of exposure to PAHs, further evidence and quantitative data are needed to illustrate the association between prenatal exposure to PAHs and CHDs. The cytochrome P450 (CYP) enzymes CYP1A1, CYP1A2, and CYP1B1 have been shown to play important roles in the metabolic activation of PAHs22. The aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor, mediates the toxic effects of a variety of environmental chemicals, including PAHs24, as well as the induction of three members of the CYP1 family, CYP1A1, CYP1A2 and CYP1B125. Few studies have investigated maternal genetic susceptibility to CHDs related to PAHs or have explored possible gene-environment interactions
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