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.
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.
- Content Type Journal Article
- Pages 1-11
- DOI 10.1007/s10803-011-1260-7
- Authors
- Stepan Melnyk, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA
- George J. Fuchs, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA
- Eldon Schulz, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA
- Maya Lopez, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA
- Stephen G. Kahler, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA
- Jill J. Fussell, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA
- Jayne Bellando, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA
- Oleksandra Pavliv, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA
- Shannon Rose, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA
- Lisa Seidel, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA
- David W. Gaylor, Department of Biostatistics, University of Arkansas for Medical Sciences, Little Rock, AR, USA
- S. Jill James, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA
- Journal Journal of Autism and Developmental Disorders
- Online ISSN 1573-3432
- Print ISSN 0162-3257