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Elevation in S‐adenosylhomocysteine and DNA hypomethylation in parents and children with autism
Author(s) -
Melnyk Stepan,
Jernigan Stefanie,
Savenka Alena,
James S. Jill
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a348-a
Subject(s) - autism , dna methylation , methyltransferase , epigenetics , methylation , homocysteine , gene , medicine , dnmt1 , endocrinology , genetics , gene expression , biology , psychiatry
Many complex developmental and neuropsychiatric disorders are influenced by gene‐environment interactions that may be mediated, in part, by aberrant DNA methylation. S‐adenosylmethionine (SAM) serves as the methyl donor for DNA methyltransferase reactions whereas the reaction product, S‐adenosylhomocysteine (SAH), is a potent product inhibitor when elevated. Recently, many autistic children were found to have impaired methylation capacity as evidenced by low SAM/SAH ratio. To further pursue these observations, we measured plasma SAM, SAH, and absolute levels of 5‐methylcystosine (5‐mC) in parents and children with autism using HPLC with electrochemical detection. Autistic children (15%) with elevated SAH and low SAM exhibited a significant decrease in absolute levels of DNA 5‐mC compared to autistic children with low SAH and normal SAM. Among the parents with elevated SAH (60%), mean SAM and homocysteine levels were not significantly different from parents with normal SAH. The 5‐mC content in DNA from parents with elevated SAH was significantly decreased relative to parents with normal SAH levels. The lack of association between elevated SAH and homocysteine levels suggests a deficiency in SAH hydrolase activity. Because DNA hypomethylation is often associated with promoter hypermethylation and abnormal gene expression, these results support a role for epigenetics in the pathophysiology of autism.