Indoor Air Pollution and Neural Tube Defects: Effect Modification by Maternal Genes

Background: Gene-environment interactions have been implicated in the development of neural tube defects (NTDs). Methods: We conducted a case-control study to investigate (1) the association of aryl hydrocarbon receptor (AHR) genetic variants and phase I metabolic enzymes with the risk of NTDs and (2) the interaction of these variants with maternal exposure to indoor air pollution from smoking and coal combustion or with placental polycyclic aromatic hydrocarbons (PAHs). Blood samples were collected from 534 mothers of fetuses or newborns with NTDs and 534 control mothers who had healthy term newborns and were assayed for 12 polymorphisms in the AHR and cytochrome P450 (CYP) genes. Information on maternal exposure was collected, and placental levels of PAHs were analyzed. Results: Maternal exposure to indoor air pollution was associated with an increased NTD risk. However, no increased NTD risk was observed for individual genetic variants. For mothers with the CYP 1B1 rs2855658 GG variant, exposure to indoor air pollution led to a doseresponse relationship for NTD risk, with odds ratios (ORs) of 3.0 (95% confidence interval = 1.6–5.7) and 8.1 (3.8–17) for medium and high levels of exposure, respectively. For mothers with G A or AA genotypes, this trend was less apparent. Placental PAHs were associated with an increased risk of NTDs, with an OR of 16 (3.3–75) for high levels compared with low levels of exposure among mothers with the GG genotype; there was no association for mothers with GA or AA genotypes. Conclusions: The CYP1B1 variant modifies the effect of indoor air pollution on NTD risk.