Authors: Stepan Melnyk George J Fuchs Eldon Schulz Maya Lopez Stephen G Kahler Jill J Fussell Jayne Bellando Oleksandra Pavliv Shannon Rose Lisa Seidel David W Gaylor S Jill James
Publish Date: 2011/04/26
Volume: 42, Issue: 3, Pages: 367-377
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 agematched 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 prooxidant environmental stressors may modulate genetic predisposition to autismThe authors would like to express their gratitude to the families in Arkansas affected by autism whose participation made this study possible We also acknowledge the invaluable help of the nurses and clinicians at the Dennis Developmental Center for referral and evaluation This research was supported in part with funding from the National Institute of Child Health and Development RO1 HD051873 SJJ the Department of Defense AS073218P1 SJJ and by grants from the Arkansas Children’s Hospital and Arkansas Biosciences Institute SJJ
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