Polymorphisms in Gene UGT1A1 Modify the Association of Prenatal Exposure to Polycyclic Aromatic Hydrocarbons With Congenital Heart Diseases Risk

Abstract Background: Previous studies have focused on the effect of polycyclic aromatic hydrocarbons (PAHs) exposure on the risk of congenital heart diseases (CHDs), but generated inconsistent conclusions. Genetic susceptibility to PAHs metabolism may modify the exposure-risk relationship. Methods: Maternal urinary biomarker of PAHs exposure was determined in 357 pregnant women with CHDs fetuses and 270 pregnant women with controls. Maternal genotyping was conducted in UGT1A1 (rs3755319, rs887829, rs4148323, rs6742078, rs6717546). Unconditional logistic regression was performed to determine the impacts of UGT1A1 polymorphisms on the risks of CHDs and its subtypes. Generalized multifactor dimensionality reduction (GMDR) was used to analyze the gene-gene and gene-PAHs exposure interactions. Results: None of the selected UGT1A1 polymorphisms were independently associated with the risk of CHDs. The interaction between rs4148323 and PAHs exposure was observed to be associated with CHDs (p<0.05). Pregnant women with high-levels PAHs exposure and carrying rs4148323 increased the risk of CHDs (GA-AA: aOR =2.00, 95% CI = 1.06-3.79). Moreover, the joint effect of rs4148323 and PAHs exposure was found to be significantly associated with risks of septal defects, conotruncal heart defects and right-sided obstructive malformations. Conclusions: Maternal genetic variation of UGT1A1 rs4148323 may modify the impact of prenatal PAHs exposure on CHDs risk. This finding needs to be further confirmed in a larger scale study.