TY - JOUR
T1 - Decreased glutathione and elevated hair mercury levels are associated with nutritional deficiency-based autism in Oman
AU - Hodgson, Nathaniel W.
AU - Waly, Mostafa I.
AU - Al-Farsi, Yahya M.
AU - Al-Sharbati, Marwan M.
AU - Al-Farsi, Omar
AU - Ali, Amanat
AU - Ouhtit, Allal
AU - Zang, Tianzhu
AU - Zhou, Zhaohui Sunny
AU - Deth, Richard C.
N1 - Funding Information:
This study was supported by the Internal Grant Fund (IG/AGR/FOOD/10/01), College of Agricultural and Marine Sciences, Sultan Qaboos University (to MIW), the Strategic Research Fund offered by His Majesty Sultan of Oman (SR/MED/FMCO/11/01), College of Medicine and Health Sciences, Sultan Qaboos University (to YMA), and grants from the NIH NIGMS (1R01GM101396 to ZSZ), American Heart Association (09PRE2300071 to T.Z.) and the Autism Research Institute (to RCD).
PY - 2014/6
Y1 - 2014/6
N2 - 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.
AB - 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.
KW - Cobalamin
KW - epigenetic
KW - folic acid
KW - homocysteine thiolactone
KW - methionine synthase
KW - neurodevelopment
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U2 - 10.1177/1535370214527900
DO - 10.1177/1535370214527900
M3 - Article
C2 - 24676906
AN - SCOPUS:84903388489
SN - 1535-3702
VL - 239
SP - 697
EP - 706
JO - Experimental Biology and Medicine
JF - Experimental Biology and Medicine
IS - 6
ER -