Risk of congenital heart diseases associated with NAT2 genetic polymorphisms and maternal polycyclic aromatic hydrocarbons exposure

Abstract

N-Acetyltransferase 2 (NAT2) is a phase II xenobiotic-metabolizing enzyme participating in the detoxification of toxic arylamines and aromatic amines. The present study was designed to investigate whether maternal NAT2 genetic polymorphisms are associated with fetal susceptibility to congenital heart diseases (CHDs) and to assess whether the risk is modified by polycyclic aromatic hydrocarbons (PAHs) exposure. We conducted a hospital-based case-control study to investigate the association of NAT2 gene polymorphisms (rs1799930 G/A, rs1208 A/G, and rs1799931 G/A) and the combinations of PAHs exposure and genetic variants with the risk of CHDs. Three hundred fifty-seven mothers of CHDs fetuses and 270 control mothers were recruited. Logistic regression models for the risk of CHDs were applied to determine the effect of NAT2 polymorphisms, as well as gene-exposure interactions. Our study did not demonstrate an association of maternal NAT2 genetic polymorphisms alone with CHDs occurrence. However, we found that certain genetic polymorphisms of NAT2 in the present of high PAHs exposure have a higher risk of CHDs. Our study suggests that the risk of CHDs associated with maternal NAT2 gene polymorphisms is potentiated by PAHs exposure.