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

被引：189
作者：
Melnyk, Stepan [1 ,2 ]
Fuchs, George J. [1 ,2 ]
Schulz, Eldon [1 ,2 ]
Lopez, Maya [1 ,2 ]
Kahler, Stephen G. [1 ,2 ]
Fussell, Jill J. [1 ,2 ]
Bellando, Jayne [1 ,2 ]
Pavliv, Oleksandra [1 ,2 ]
Rose, Shannon [1 ,2 ]
Seidel, Lisa [1 ,2 ]
Gaylor, David W. [3 ]
James, S. Jill [1 ,2 ]
机构：
[1] Arkansas Childrens Hosp, Res Inst, Dept Pediat, Little Rock, AR 72202 USA
[2] Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72205 USA
[3] Univ Arkansas Med Sci, Dept Biostat, Little Rock, AR 72205 USA
来源：
JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS | 2012年 / 42卷 / 03期
关键词：
Autism; Oxidative stress; Metabolic; Epigenetics; Glutathione; DNA methylation; PERFORMANCE LIQUID-CHROMATOGRAPHY; ONE-CARBON METABOLISM; DNA-METHYLATION; ELECTROCHEMICAL DETECTION; GLUTATHIONE DISULFIDE; S-ADENOSYLMETHIONINE; PROFILING REVEALS; REDOX REGULATION; SCHIZOPHRENIA; MODEL;
D O I：
10.1007/s10803-011-1260-7
中图分类号：
B844 [发展心理学（人类心理学）];
学科分类号：
040202 ;
摘要：
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.
引用
收藏
页码：367 / 377
页数：11
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