Abstract
DNA methylation is mediated by DNA methyltransferases (DNMTs) that add a methyl group to the 5′-carbon of cytosine. The enzyme methylenetetrahydrofolate reductase (MTHFR) catalyzes the reduction of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate in the rate-limiting step of the cycle involving the methyl donor S-adenosyl-L-methionine (SAM). The MTHFR C677T polymorphism results in a thermolabile enzyme with reduced activity that is predicted to influence the DNA methylation status. In this study, we investigated the impact of the MTHFR C677T polymorphism on the global DNA methylation of oral epithelial cells obtained from 54 healthy subjects. There were no significant differences in global DNA methylation among the MTHFR CC, CT and TT genotypes (p = 0.75; Kruskal-Wallis test).
Highlights
DNA methylation is dependent on a methyl donor and S-adenosyl-L-methionine (SAM) is the primary methyl group donor for most biological methylation reactions (Chiang et al, 1996)
After donating the methyl group, 5-methyltetrahydrofolate is converted to tetrahydrofolate and to 5,10-methylenetetrahydrofolate by serine hydroxymethyltransferase. 5,10-methylenetetrahydrofolate is a key substrate that can be directed towards nucleotide biosynthesis or methionine regeneration
The methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism has been suspected to induce hypomethylation and activate proto-oncogenes, which could explain the association between this polymorphism and some types of cancer
Summary
DNA methylation is dependent on a methyl donor and S-adenosyl-L-methionine (SAM) is the primary methyl group donor for most biological methylation reactions (Chiang et al, 1996). Even within the same age group, gender and cell types, inter-individual variations are still observed and are influenced by environmental and genetic factors (Valenza-Schaerly et al, 2001; Weaver et al, 2004; Fraga et al, 2005; Sinclair et al, 2007; Bjornsson et al, 2008). The aim of this study was to assess the influence of the MTHFR C677T polymorphism on global DNA methylation in oral epithelial cells in young subjects with no systemic disorders or visible alterations in the oral mucosa.
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