ESR1基因多态性与儿童孤独症的关联研究

Purpose: Autism spectrum disorders (ASD) are a group of neurodevelopment conditions with significant sex differences. Previous studies supported that fetal testosterone exposures might be a strong factor of ASD. As aromatization of testosterone, estrogens play a crucially important role in early nervous system development and sex differentiation through estrogen receptors in animal brain. Several reports have described that single nucleotide polymorphisms (SNPs) of estrogen receptor alpha (ESR1) are associated with psychiatric disorders such as depression and schizophrenia. However, the investigation of ESR1 effected in autism has been neglected. Therefore, we tested the hypothesis that ESR1 gene is involved in the pathogenesis of autism and clinical symptoms. Methods: Genotypes rs11155819 and rs2234693 were determined in 117 children with classic autism and 117 normal children from Chinese Han population. A case-control study was performed to explore the association between ESR1 gene variants and autism susceptibility. The Children Autism Rating Scale (CARS) and Neuropsychological development examination table for children aged 0-6 years old were used, respectively, to evaluate autism severity and the developmental level. Finally, we analyzed the association of these SNPs with specific clinical symptoms. Results: The distribution of genotypes and allele frequencies of rs11155819 and rs2234693 showed no significant differences between classic autism cases and normal healthy controls. However, individuals with rs11155819 T/T genotype showed a higher CARS score, a lower value for fine motor and adaptation ability in development quotient (DQ) (p = 0.033; p = 0.032; p = 0.045). Individuals with rs2234693 T/T genotype had lower values for social behavior in DQ (p = 0.012). Conclusion: Results suggest that ESR1 variants are relevant to autism severity and clinical symptoms in the Chinese Han population.