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Autism Spectrum Disorder: Interaction of Air Pollution with the MET Receptor Tyrosine Kinase Gene

Volk, Heather E.a,b,c; Kerin, Taraa; Lurmann, Fredd; Hertz-Picciotto, Irvae; McConnell, Roba; Campbell, Daniel B.c,f,g

doi: 10.1097/EDE.0000000000000030
Air Pollution

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.

Supplemental Digital Content is available in the text.

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.

F.L. is an employee of Sonoma Technology Inc., Petaluma, CA. R.M.C. received support from an air quality violations settlement agreement between the South Coast Air Quality Management District, a California state regulatory agency, and BP. H.E.V. received travel funds from Autism Speaks to present a paper at an academic conference. The other authors declare no competing financial interests.

Supported by NIEHS; ES019002, ES013578, ES007048, ES11269, ES015359, ES016535, and ES011627; EPA Star-R; 823392, 833292; and MIND Institute matching funds and pilot grant program.

Supplemental digital content is available through direct URL citations in the HTML and PDF versions of this article ( This content is not peer-reviewed or copy-edited; it is the sole responsibility of the author.

Correspondence: Heather E. Volk, University of Southern California, 2001 N. Soto Street, MC 9237, Los Angeles, CA 90089. E-mail:

© 2014 by Lippincott Williams & Wilkins, Inc