Gene-environment interactions between air pollution and biotransformation enzymes and risk of birth defects

Abstract

Background: Genetic factors and environmental factors have been observed to influence risks for birth defects. Few studies have investigated gene-environment interactions that could contribute to birth defects. Our aim was to examine the interaction between gene variants in biotransformation enzyme pathways and ambient air pollution exposures and risk of several structural birth defects.Methods: We evaluated the role of ambient air pollutant exposure [nitrogen dioxide (NO2), nitrogen oxide, carbon monoxide, particulate matter <10 (PM10) and <2.5 (PM2.5) microns] during pregnancy and 104 gene variants of biotransformation enzymes from infant bloodspots or buccal cells in a California population-based case-control (409 cases and 208 nonmalformed controls) study. Cases included cleft lip with or without cleft palate (N=206), gastroschisis (N=94), tetralogy of Fallot (N=69) and dextro-transposition of the great arteries (d-TGA; N=40). We considered race/ethnicity and folic acid vitamin use as potential effect modifiers and adjusted for smoking.Results: We observed increased risk of d-TGA associated with interactions between CYP2A6 and NO2 (OR=7.1), SLCO1B1 and NO2 (OR=4.0), NAT2 and PM10 (OR=3.5), SLCO1B1 and PM10 (OR=3.0), SLCO2B1 and PM10 (OR=4.4). We also observed gene-environment interactions for cleft lip with or without cleft palate (CYP2D6 and PM10; OR=2.8), gastroschisis (CYP2C9 and PM10; OR=4.2) and tetralogy of Fallot (NAT2 and PM2.5; OR=5.0). Conclusions: These analyses show interactions between air pollution exposure during early pregnancy and gene variants associated with metabolizing enzymes with regard to risk of d-TGA, though results were less consistent for other birth defects. These exploratory results suggest that some individuals based on their genetic background may be more susceptible to the adverse effects of air pollution.