BACKGROUND: Hyperhomocysteinaemia occurs in several genetically determined and acquired disorders and is highly prevalent in @entity1 with uraemia. In these disorders, @entity1255 precursor @entity13710 , a powerful competitive inhibitor of @entity7726 -dependent methyltransferases, is increased, suggesting unbalanced methylation. We aimed to investigate whether DNA hypomethylation is present in @entity1 with uraemia who also have hyperhomocysteinaemia and whether regulation of specific classes of genes, dependent on DNA methylation, is compromised. METHODS: We selected @entity1 with hyperhomocysteinaemia and uraemia who were having standard haemodialysis treatment, and compared them with healthy male controls. We measured the @entity1255 concentration from plasma samples and obtained DNA and RNA samples from peripheral mononuclear cells. DNA methylation was assessed by @entity5538 extension assay and by Southern blotting. Allelic expression of pseudoautosomal and imprinted genes was investigated by analysis of suitable restriction fragment length polymorphisms. FINDINGS: Total DNA hypomethylation was higher in @entity1 than in controls (z score -4.593, p=0.0006) and allelic expression was changed in both sex-linked and imprinted genes. The shift from monoallelic to biallelic expression was dependent on @entity1255 concentrations. @entity1501 therapy, a common method to reduce hyperhomocysteinaemia, restored DNA methylation to normal levels and corrected the patterns of gene expression. INTERPRETATION: Our results suggest that hyperhomocysteinaemia affects epigenetic control of gene expression, which can be reverted by @entity1501 treatment. Our data support the hypothesis that the toxic action of @entity1255 can be mediated by macromolecule hypomethylation.

XXXX treatment and unbalanced methylation and changes of allelic expression induced by hyperhomocysteinaemia in @entity1 with uraemia.

@entity1 :: ('9606', 'Species') :: ['patients', 'men'] @entity1501 :: ('MESH:D005492', 'Chemical') :: ['Folate', 'folate'] @entity1255 :: ('MESH:D006710', 'Chemical') :: ['homocysteine'] @entity13710 :: ('MESH:D012435', 'Chemical') :: ['S-adenosylhomocysteine'] @entity7726 :: ('MESH:D012436', 'Chemical') :: ['S-adenosylmethionine'] @entity5538 :: ('MESH:D003596', 'Chemical') :: ['cytosine']
@entity1501 :: (MESH:D005492,Chemical) :: ['Folate']
