Autism spectrum disorder: interaction of air pollution with the MET receptor tyrosine kinase gene.
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.
From the aDepartment of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA; bDepartment of Pediatrics, Children's Hospital Los Angeles, University of Southern California, Los Angeles, CA; cZilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA; dSonoma Technology, Inc., Petaluma, CA; eDepartment of Public Health Sciences, University of California, Davis, Davis, CA; fDepartment of Psychiatry and the Behavioral Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA; and gCenter for Genomic Psychiatry, Keck School of Medicine, University of Southern California, Los Angeles, CA.
Heather E
HE
Volk
Tara
T
Kerin
Fred
F
Lurmann
Irva
I
Hertz-Picciotto
Rob
R
McConnell
Daniel B
DB
Campbell
D000397:Air Pollution / Q000706:statistics & numerical data*; D016022:Case-Control Studies; D002659:Child Development Disorders, Pervasive / Q000453:epidemiology / Q000235:genetics*; D002675:Child, Preschool; D004781:Environmental Exposure; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D009585:Nitrogen Dioxide; D010126:Ozone; D052638:Particulate Matter; D020641:Polymorphism, Single Nucleotide; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics*; D012307:Risk Factors; D001335:Vehicle Emissions
D052638:Particulate Matter; D001335:Vehicle Emissions; D010126:Ozone; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met; D009585:Nitrogen Dioxide