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 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.

Disrupted nocturnal melatonin in autism: Association with tumor necrosis factor and sleep disturbances

“…As TNF and other pro‐inflammatory cytokines can increase indoleamine 2,3‐dioxygenase (IDO), leading to tryptophan being driven down the kynurenine pathway and away from serotonin and melatonin synthesis, 4 it will be important to determine IDO and kynurenine pathway products in correlation with TNF, and aMT6s in future research. Given the alterations in the kynurenine pathway in ASD, 69 and the ability of kynurenine and kynurenic acid to activate the aryl hydrocarbon receptor (AhR), a susceptibility gene for ASD severity, 70 the integration of the kynurenine pathway, AhR, and their impacts on neuronal and immune system function with the immune‐pineal axis will be important to evaluate.…”

Gut Microbiota Regulation of Tryptophan Metabolism in Health and Disease

“…Total neuroprotective metabolites such as picolinic acid (PA), a metabolite of the KP, are decreased in ASD patients despite an excess of QA production (Lim et al, 2016). Moreover, AhR signaling might also be involved, as polymorphisms in the gene encoding AhR nuclear translocator (ARNT), which binds and facilitates AhR functions, are associated with ASD severity (Fujisawa et al, 2016).…”

The role of the microbiota-gut-brain axis in neuropsychiatric disorders

“…In contrast, the hippocampi of bipolar disorder patients displayed marked changes in glucose metabolism. 72 Another study found an association between AhR-related gene variants and ASD severity 73 (for more details, see Figure 2 ).…”