title: Metabolic imbalance associated with methylation dysregulation and oxidative damage in children with autism.
abstract: Oxidative stress and abnormal DNA methylation have been implicated in the pathophysiology of autism. We investigated the dynamics of an integrated metabolic pathway essential for cellular antioxidant and methylation capacity in 68 children with autism, 54 age-matched control children and 40 unaffected siblings. The metabolic profile of unaffected siblings differed significantly from case siblings but not from controls. Oxidative protein/DNA damage and DNA hypomethylation (epigenetic alteration) were found in autistic children but not paired siblings or controls. These data indicate that the deficit in antioxidant and methylation capacity is specific for autism and may promote cellular damage and altered epigenetic gene expression. Further, these results suggest a plausible mechanism by which pro-oxidant environmental stressors may modulate genetic predisposition to autism.
authors.affiliation: Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72202, USA.
authors.forename: Stepan
authors.initials: S
authors.lastname: Melnyk
authors.forename: George J
authors.initials: GJ
authors.lastname: Fuchs
authors.forename: Eldon
authors.initials: E
authors.lastname: Schulz
authors.forename: Maya
authors.initials: M
authors.lastname: Lopez
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Kahler
authors.forename: Jill J
authors.initials: JJ
authors.lastname: Fussell
authors.forename: Jayne
authors.initials: J
authors.lastname: Bellando
authors.forename: Oleksandra
authors.initials: O
authors.lastname: Pavliv
authors.forename: Shannon
authors.initials: S
authors.lastname: Rose
authors.forename: Lisa
authors.initials: L
authors.lastname: Seidel
authors.forename: David W
authors.initials: DW
authors.lastname: Gaylor
authors.forename: S Jill
authors.initials: SJ
authors.lastname: James
mesh_terms: D001321:Autistic Disorder / Q000378:metabolism*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D019175:DNA Methylation; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008297:Male; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D005978:Glutathione