title: DNA Methylation Analysis of HTR2A Regulatory Region in Leukocytes of Autistic Subjects.
abstract: Disturbed brain and peripheral serotonin homeostasis is often found in subjects with autism spectrum disorder (ASD). The role of the serotonin receptor 2A (HTR2A) in the regulation of central and peripheral serotonin homeostasis, as well as its altered expression in autistic subjects, have implicated the HTR2A gene as a major candidate for the serotonin disturbance seen in autism. Several studies, yielding so far inconclusive results, have attempted to associate autism with a functional SNP -1438 G/A (rs6311) in the HTR2A promoter region, while possible contribution of epigenetic mechanisms, such as DNA methylation, to HTR2A dysregulation in autism has not yet been investigated. In this study, we compared the mean DNA methylation within the regulatory region of the HTR2A gene between autistic and control subjects. DNA methylation was analysed in peripheral blood leukocytes using bisulfite conversion and sequencing of the HTR2A region containing rs6311 polymorphism. Autistic subjects of rs6311 AG genotype displayed higher mean methylation levels within the analysed region than the corresponding controls (P < 0.05), while there was no statistically significant difference for AA and GG carriers. Our study provides preliminary evidence for increased HTR2A promoter methylation in leukocytes of a portion of adult autistic subjects, indicating that epigenetic mechanisms might contribute to HTR2A dysregulation observed in individuals with ASD.
authors.affiliation: Department of Animal Physiology, Division of Biology, Faculty of Science, University of Zagreb, Zagreb, Croatia.
authors.forename: Dubravka
authors.initials: D
authors.lastname: Hranilovic
authors.affiliation: Department of Animal Physiology, Division of Biology, Faculty of Science, University of Zagreb, Zagreb, Croatia.
authors.forename: Sofia
authors.initials: S
authors.lastname: Blazevic
authors.affiliation: Laboratory of Neurochemistry and Molecular Neurobiology, Division of Molecular Biology, Rudjer Boskovic Institute, Zagreb, Croatia.|Catholic University of Croatia, Zagreb, Croatia.
authors.forename: Jasminka
authors.initials: J
authors.lastname: Stefulj
authors.affiliation: Division of Psychiatric Genetics and Neurochemistry, Department of Psychiatry and Psychotherapy, Ludwig-Maximilian University of Munich, Munich, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Zill
mesh_terms: D000293:Adolescent; D000328:Adult; D001321:Autistic Disorder / Q000097:blood* / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D007962:Leukocytes; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics*; D055815:Young Adult
chemical_list: D044402:Receptor, Serotonin, 5-HT2A
keywords: DNA methylation; HTR2A; autism; epigenetics; serotonin