Methylenetetrahydrofolate reductase C677T and methionine synthase A2756G polymorphisms influence on leukocyte genomic DNA methylation level.
As both MTR and MTHFR are enzymes involved in the production of methyl groups, Weiner et al (2014) wished to examine the effects of a their gene mutations on levels of DNA methylation within leukocytes. As the C677T MTHFR mutation is has been well studied in affecting DNA methylation, the authors wished to uncover the effect of the gene mutation A2756G found in the Methionine Synthase (MTR) enzyme independent of MTHFR. 80 people with the wild type of the gene, 2756AA where examined alongside 80 people with the homozygous mutation of the gene, 2756GG. The same occurred with the MTHFR 677CC and 677TT mutations.
The level of DNA methylation within each group was then analysed. In comparison to the 2756AA mutation, those with the homozygous 2756GG mutation showed higher levels of DNA methylation. However those with the 677CC wild type had higher levels of DNA methylation compared to those with the 677TT mutation. Overall, the data provides evidence that the MTR 2756GG increases the level of methylation, while the MTHFR C67TT mutation decreases the level of DNA methylation.