Association of Aryl Hydrocarbon Receptor-Related Gene Variants with the Severity of Autism Spectrum Disorders
Association of Aryl Hydrocarbon Receptor-Related Gene Variants with the Severity of Autism Spectrum Disorders
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DOI：
10.3389/fpsyt.2016.00184
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发表时间：
2016-11-16
影响因子：
4.7
通讯作者：
Shinohara, Kazuyuki
中科院分区：
文献类型：
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作者：
Fujisawa, Takashi X.;Nishitani, Shota;Shinohara, Kazuyuki
暴露于环境化学物质，如二恶英，已知对性腺类固醇的稳态有不利影响，从而可能改变大脑的性别分化以表达自闭症特征。二恶英类化合物作用于芳香烃受体（AhR），AhR相关基因的多态性和突变可能对大脑的性别分化产生病理影响，导致自闭症特征。为了探讨AhR相关基因多态性与孤独症易感性的关系，我们鉴定了患者和对照组中AhR相关基因的基因型，并确定了两组之间是否存在不同的基因和基因型分布。此外，为了阐明多态性与自闭症严重程度之间的关系，我们比较了AhR相关基因的两种基因型（rs2066853，rs2228099）与自闭症症状的严重程度。虽然在自闭症谱系障碍（ASD）患者和对照个体之间没有发现本文研究的任何多态性的基因型分布的统计学显著差异，但在rs2228099多态性中观察到严重程度的总评分的显著差异，表明多态性改变ASD症状的严重程度，但不改变ASD易感性。此外，我们还发现，严重程度的社会沟通评分存在显著差异。这些结果表明，rs2228099多态性可能与社会沟通障碍的严重程度在不同的ASD症状。
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 of AhR-related gene may exert pathological influences on sexual differentiation of the brain, causing autistic traits. To ascertain the relationship between AhR-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 of AhR-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.