自闭症儿童中与甲基化失调和氧化损伤相关的代谢失衡。
Metabolic imbalance associated with methylation dysregulation and oxidative damage in children with autism.
机构信息
Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72202, USA.
出版信息
J Autism Dev Disord. 2012 Mar;42(3):367-77. doi: 10.1007/s10803-011-1260-7.
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.
摘要
氧化应激和异常的 DNA 甲基化与自闭症的病理生理学有关。我们研究了一个对细胞抗氧化和甲基化能力至关重要的综合代谢途径在 68 名自闭症儿童、54 名年龄匹配的对照儿童和 40 名未受影响的兄弟姐妹中的动态变化。未受影响的兄弟姐妹的代谢特征与病例兄弟姐妹明显不同，但与对照组没有差异。在自闭症儿童中发现了氧化蛋白/DNA 损伤和 DNA 低甲基化（表观遗传改变），但在配对的兄弟姐妹或对照组中没有发现。这些数据表明，抗氧化和甲基化能力的缺陷是自闭症特有的，可能会导致细胞损伤和表观遗传基因表达改变。此外，这些结果表明了一种合理的机制，即促氧化剂环境应激物可能调节自闭症的遗传易感性。
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