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Methylation Rates with Mutated MTHFR and MTR Genes

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.

The MTHFR gene is involved in converting folates into the active 5methylfolate, with the MTR gene involved in the donation of a methyl group from folate to B12 within the Methionine/ Homocysteine cycle.

As the C677T MTHFR mutation is has been well studied in affecting DNA methylation, the authors focused on the effects of MTR gene mutations on methylation levels. One group comprised of wild type MTR 2756AA genotype were compared against another group with equal numbers of people with the homozygous MTR 2756GG genotype.

Results found DNA methylation was higher in those with the homozygous 2756GG MTR mutation when compared to those with the normal 2756AA genotype. Conversely, those with the normal 677CC genotype had higher levels of DNA methylation when compared to those with the homozygous 677TT mutation.

This research highlights the differences in methylation that difference genetic mutations can create within the methylation cycle. The MTHR 2756GG polymorphism is show to increase methylation, whilst the 677TT mutation decreases methylation. Any deviation from appropriate levels of methylation can lead to dysfunction within the cells, and hence tissue.

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