Association between single nucleotide polymorphisms in estrogen receptor 1/2 genes and symptomatic severity of autism spectrum disorder.

BACKGROUND: Previous studies on etiology of autism spectrum disorders (ASD) have shown strong contribution of hereditary factors. On the basis the heterogeneity in ASD symptoms, it is highly possible that each independent domain of ASD symptom is linked to a different set of genetic risk factors. However, few empirical investigations have been carried out to examine this hypothesis. AIMS: The aim of the present study was to investigate the association between single-nucleotide polymorphisms (SNPs) in estrogen receptor genes, which several previous studies have identified as potential risk factors of ASD, and the severity of each independent aspect of ASD symptom within an Asian clinical sample. METHOD AND PROCEDURES: We investigated the association between severities of four ASD symptoms (Social Communication, Social Interaction, Stereotypies and Sensory Abnormalities, and Emotional Regulation) measured by childhood autism rating scale and SNPs in genes of estrogen receptor 1 and 2, ESR1 rs11155819 and ESR2 rs1152582, in 96 Japanese individuals with ASD. OUTCOMES AND RESULTS: The analysis revealed that severities in the impairment of social interaction and emotional regulation were linked to SNPs in ESR1 rs11155819 and ESR2 rs1152582, respectively. The effect of genotype was not observed for the other aspects of ASD symptoms. CONCLUSIONS AND IMPLICATIONS: These findings support our contention that the severity of each ASD symptom domain is determined by a distinct set of genetic risk factors.

Association of Aryl Hydrocarbon Receptor-Related Gene Variants with the Severity of Autism Spectrum Disorders.

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.

Characteristics of the sensory-motor, verbal and cognitive abilities of preschool boys with attention deficit/hyperactivity disorder combined type.

The purpose of this study is to clarify the characteristics of sensory-motor, verbal and cognitive abilities of preschool boys with attention-deficit/hyperactivity disorder (ADHD) in order to provide information for their treatment and education at preschool age by teachers and professionals. For this purpose, 46 Japanese boys with ADHD-combined type (ADHD-C) whose ages ranged from 45 to 72 months were examined using the Japanese version of the Miller Assessment for Preschoolers (JMAP), and were compared with 46 Japanese boys matched for age and gender in the normative samples that served as the standardizations for the JMAP. The results showed that the ADHD-C group was significantly lower than the normative sample group both on the Total score and on each Index score (P < 0.01) with the exception of the Non-verbal Index. In particular, the number of boys with ADHD-C scoring below the 5th percentile on the Foundation Index (i.e. fundamental sensory-motor tests) was the highest among all index scores. The ADHD-C group had significantly lower scores than the normative sample group in equilibrium, postural control, fine motor of hand and tongue, motor praxis, articulation, memory related to the comprehension of long sentences, and visual construction. Because fundamental sensory-motor abilities were notably lower in the ADHD-C group than in the normative sample group, it is suggested that preschool boys with ADHD-C should be examined and treated for sensory-motor disabilities.