Abstract
Autism spectrum disorder (ASD) is a neurodevelopment disorder with abnormalities of social interaction, communication and repetitive behaviors. The higher prevalence of ASD in men implies a potential relationship between sex hormones and ASD etiology. The ESR2 gene encodes estrogen receptor beta (ESR2) and plays an important role during brain development. A relationship between ESR2 and ASD has been suggested by studies on single nucleotide polymorphisms and mRNA and protein expression levels in ASD patients. Here, we explored the possible epigenetic regulation of the ESR2 gene in autism. We collected genomic DNA from the peripheral blood of Chinese Han males with autism and age-matched normal males and measured DNA methylation of CpG islands in the ESR2 gene, which consisted of 41 CpG sites among the proximal promoter region and an untranslated exon, by bisulfite sequencing. We also investigated a relationship between DNA methylation and phenotypic features of autism, as assessed by the Children Autism Rating Scale. We found little overall difference in the DNA methylation of the ESR2 5′-flanking region in individuals with autism compared with normal individuals. However, detailed analyses revealed that eight specific CpG sites were hypermethylated in autistic individuals and that four specific CpG sites were positively associated with the severity of autistic symptoms. Our study indicates that the epigenetic dysregulation of ESR2 may govern the development of autism.
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Acknowledgements
We thank Dr. Mayumi Oda (Keio University) for the advice on BSP. We thank all members of the laboratory for helpful discussions. This work was supported by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan (M.N. and N.S.), the National Natural Science Foundation of China (81202221 to S.L.), and the Education Department of Heilongjiang Province (12521232 to S.L.).
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This study was funded by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan (M.N. and N.S.), the National Natural Science Foundation of China (81202221 to S.L.), and the Education Department of Heilongjiang Province (12521232 to S.L.).
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The authors declare that they have no conflict of interest.
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“All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.”
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Wang, X., Liang, S., Sun, Y. et al. Analysis of estrogen receptor β gene methylation in autistic males in a Chinese Han population. Metab Brain Dis 32, 1033–1042 (2017). https://doi.org/10.1007/s11011-017-9990-7
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DOI: https://doi.org/10.1007/s11011-017-9990-7