Hodgson Nathaniel W, Waly Mostafa I, Al-Farsi Yahya M, Al-Sharbati Marwan M, Al-Farsi Omar, Ali Amanat, Ouhtit Allal, Zang Tianzhu, Zhou Zhaohui Sunny, Deth Richard C
Exp Biol Med (Maywood). 2014 Jun;239(6):697-706. doi: 10.1177/1535370214527900.
Genetic, nutrition, and environmental factors have each been implicated as sources of risk for autism. Oxidative stress, including low plasma levels of the antioxidant glutathione, has been reported by numerous autism studies, which can disrupt methylation-dependent epigenetic regulation of gene expression with neurodevelopmental consequences. We investigated the status of redox and methylation metabolites, as well as the level of protein homocysteinylation and hair mercury levels, in autistic and neurotypical control Omani children, who were previously shown to exhibit significant nutritional deficiencies in serum folate and vitamin B₁₂. The serum level of glutathione in autistic subjects was significantly below control levels, while levels of homocysteine and S-adenosylhomocysteine were elevated, indicative of oxidative stress and decreased methionine synthase activity. Autistic males had lower glutathione and higher homocysteine levels than females, while homocysteinylation of serum proteins was increased in autistic males but not females. Mercury levels were markedly elevated in the hair of autistic subjects vs. control subjects, consistent with the importance of glutathione for its elimination. Thus, autism in Oman is associated with decreased antioxidant resources and decreased methylation capacity, in conjunction with elevated hair levels of mercury.
遗传、营养和环境因素均被认为是自闭症的风险来源。众多自闭症研究报告称,存在氧化应激,包括血浆中抗氧化剂谷胱甘肽水平较低,这会破坏依赖甲基化的基因表达表观遗传调控,进而产生神经发育方面的后果。我们调查了患有自闭症的阿曼儿童和作为对照的发育正常的阿曼儿童体内氧化还原和甲基化代谢物的状况,以及蛋白质高半胱氨酸化水平和头发汞含量,这些儿童先前已被证明血清叶酸和维生素B₁₂存在显著营养缺乏。自闭症患者的血清谷胱甘肽水平显著低于对照组,而同型半胱氨酸和S -腺苷同型半胱氨酸水平升高,表明存在氧化应激且甲硫氨酸合成酶活性降低。自闭症男性的谷胱甘肽水平低于女性,同型半胱氨酸水平高于女性,而自闭症男性血清蛋白的高半胱氨酸化增加,女性则不然。与对照组相比,自闭症患者头发中的汞含量显著升高,这与谷胱甘肽对汞消除的重要性相符。因此,阿曼的自闭症与抗氧化资源减少、甲基化能力降低以及头发汞含量升高有关。