Abstract
BACKGROUND: Independent studies report association of autism spectrum disorder with air pollution exposure and a functional promoter variant (rs1858830) in the MET receptor tyrosine kinase (MET) gene. Toxicological data find altered brain Met expression in mice after prenatal exposure to a model air pollutant. Our objective was to investigate whether air pollution exposure and MET rs1858830 genotype interact to alter the risk of autism spectrum disorder. METHODS: We studied 252 cases of autism spectrum disorder and 156 typically developing controls from the Childhood Autism Risk from Genetics and the Environment Study. Air pollution exposure was assigned for local traffic-related sources and regional sources (particulate matter, nitrogen dioxide, and ozone). MET genotype was determined by direct resequencing. RESULTS: Subjects with both MET rs1858830 CC genotype and high air pollutant exposures were at increased risk of autism spectrum disorder compared with subjects who had both the CG/GG genotypes and lower air pollutant exposures. There was evidence of multiplicative interaction between NO2 and MET CC genotype (P= 0.03). CONCLUSIONS: MET rs1858830 CC genotype and air pollutant exposure may interact to increase the risk of autism spectrum disorder.