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Metabolic Imbalance Associated with Methylation Dysregulation and Oxidative Damage in Children with Autism

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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.

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Acknowledgments

The 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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  1. Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA

    Stepan Melnyk, George J. Fuchs, Eldon Schulz, Maya Lopez, Stephen G. Kahler, Jill J. Fussell, Jayne Bellando, Oleksandra Pavliv, Shannon Rose, Lisa Seidel & S. Jill James

  2. Department of Biostatistics, University of Arkansas for Medical Sciences, Little Rock, AR, USA

    David W. Gaylor

  3. Department of Pediatrics, Arkansas Children’s Hospital Research Institute, 13 Children’s Way, Slot 512-41B, Little Rock, AR, 72202, USA

    Stepan Melnyk, George J. Fuchs, Eldon Schulz, Maya Lopez, Stephen G. Kahler, Jill J. Fussell, Jayne Bellando, Oleksandra Pavliv, Shannon Rose, Lisa Seidel & S. Jill James

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Melnyk, S., Fuchs, G.J., Schulz, E. et al. Metabolic Imbalance Associated with Methylation Dysregulation and Oxidative Damage in Children with Autism. J Autism Dev Disord 42, 367–377 (2012). https://doi.org/10.1007/s10803-011-1260-7

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