title: Analysis of estrogen receptor β gene methylation in autistic males in a Chinese Han population.
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.
authors.affiliation: Department of Child and Adolescent Health, School of Public Health, Harbin Medical University, No.157 Baojian Road, Harbin, 150081, China.|Department of Pediatrics, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan.
authors.forename: Xuelai
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Child and Adolescent Health, School of Public Health, Harbin Medical University, No.157 Baojian Road, Harbin, 150081, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Liang
authors.affiliation: Department of Child and Adolescent Health, School of Public Health, Harbin Medical University, No.157 Baojian Road, Harbin, 150081, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Child and Adolescent Health, School of Public Health, Harbin Medical University, No.157 Baojian Road, Harbin, 150081, China.
authors.forename: Haixin
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Pediatrics, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan.
authors.forename: Fumio
authors.initials: F
authors.lastname: Endo
authors.affiliation: Department of Medical Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto, 860-0811, Japan.
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Nakao
authors.affiliation: Department of Medical Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto, 860-0811, Japan. norikos@kumamoto-u.ac.jp.|Department of Cancer Biology, The Cancer Institute of JFCR, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan. norikos@kumamoto-u.ac.jp.
authors.forename: Noriko
authors.initials: N
authors.lastname: Saitoh
authors.affiliation: Department of Child and Adolescent Health, School of Public Health, Harbin Medical University, No.157 Baojian Road, Harbin, 150081, China. wulijiehyd@126.com.
authors.forename: Lijie
authors.initials: L
authors.lastname: Wu
mesh_terms: D044466:Asian People / Q000235:genetics; D001321:Autistic Disorder / Q000235:genetics*; D002675:Child, Preschool; D002681:China; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D047629:Estrogen Receptor beta / Q000235:genetics*; D006801:Humans; D008297:Male; D011401:Promoter Regions, Genetic
chemical_list: D047629:Estrogen Receptor beta
keywords: Autism; DNA methylation; Estrogen receptor beta; Promoter