title: Association of Aryl Hydrocarbon Receptor-Related Gene Variants with the Severity of Autism Spectrum Disorders.
abstract: Exposure to environmental chemicals, such as dioxin, is known to have adverse effects on the homeostasis of gonadal steroids, thereby potentially altering the sexual differentiation of the brain to express autistic traits. Dioxin-like chemicals act on the aryl hydrocarbon receptor (AhR), polymorphisms, and mutations ofAhR-related gene may exert pathological influences on sexual differentiation of the brain, causing autistic traits. To ascertain the relationship betweenAhR-related gene polymorphisms and autism susceptibility, we identified genotypes of them in patients and controls and determined whether there are different gene and genotype distributions between both groups. In addition, to clarify the relationships between the polymorphisms and the severity of autism, we compared the two genotypes ofAhR-related genes (rs2066853, rs2228099) with the severity of autistic symptoms. Although no statistically significant difference was found between autism spectrum disorder (ASD) patients and control individuals for the genotypic distribution of any of the polymorphisms studied herein, a significant difference in the total score of severity was observed in rs2228099 polymorphism, suggesting that the polymorphism modifies the severity of ASD symptoms but not ASD susceptibility. Moreover, we found that a significant difference in the social communication score of severity was observed. These results suggest that the rs2228099 polymorphism is possibly associated with the severity of social communication impairment among the diverse ASD symptoms.
authors.affiliation: Department of Neurobiology and Behavior, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan; Research Center for Child Mental Development, University of Fukui, Fukui, Japan.
authors.forename: Takashi X
authors.initials: TX
authors.lastname: Fujisawa
authors.affiliation: Department of Neurobiology and Behavior, Graduate School of Biomedical Sciences, Nagasaki University , Nagasaki , Japan.
authors.forename: Shota
authors.initials: S
authors.lastname: Nishitani
authors.affiliation: Department of Occupational Therapy, Graduate School of Health Sciences, Nagasaki University , Nagasaki , Japan.
authors.forename: Ryoichiro
authors.initials: R
authors.lastname: Iwanaga
authors.affiliation: Nagasaki Municipal Welfare Center for the Handicapped , Nagasaki , Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Matsuzaki
authors.affiliation: Sasebo Child Development Center , Sasebo , Japan.
authors.forename: Chisato
authors.initials: C
authors.lastname: Kawasaki
authors.affiliation: Department of Neuropsychiatry, Teikyo University School of Medicine , Tokyo , Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Tochigi
authors.affiliation: Department of Physical and Health Education, Graduate School of Education, The University of Tokyo , Tokyo , Japan.
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Sasaki
authors.affiliation: Medical Institute of Developmental Disabilities Research, Showa University , Tokyo , Japan.
authors.forename: Nobumasa
authors.initials: N
authors.lastname: Kato
authors.affiliation: Department of Neurobiology and Behavior, Graduate School of Biomedical Sciences, Nagasaki University , Nagasaki , Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Shinohara
keywords: aryl hydrocarbon receptor; aryl hydrocarbon receptor nuclear translocator; autism spectrum disorder; polymorphism; severity; social communication