MTR 2756 A>G
Allele frequency in population
The 1000 Genomes Project Database reports a global frequency of 21% for the G allele (NIH).
Gene and SNP Summary
MTR encodes the enzyme, Methionine Synthase, which catalyzes the remethylation of homocysteine to methionine. The G allele is associated with increased activity of the enzyme and thus influences the level of circulating homocysteine. The SNP has been linked with fewer vascular events than would generally be expected, and thus could be considered to be a beneficial, protective SNP.
MTR Gene Detail
MTR encodes the vitamin B12 dependent enzyme, methionine synthase. This enzyme is responsible for the irreversible remethylation of homocysteine to methionine, using 5-methyl tetrahydrofolate as a cofactor. This reaction is essential in maintaining healthy levels of homocysteine and a healthy ratio of SAM:SAH.
MTR 2756 A>G
There is a common polymorphism which affects the functional site of the protein and hence the levels of circulating folate and homocysteine. Homocysteine levels tend to be lower in the presence of the polymorphism (G allele), and there is a dose-dependent decline across AA, AG and GG genotypes. It appears that the polymorphism increases the activity of the enzyme, enhancing the conversion of homocysteine to Methionine, and reducing homocysteine levels; this is thus a beneficial variant.
In addition to lowering homocysteine levels, it has been found that AG individuals have fewer vascular events than would be expected. The AG genotype is also a significant predictor for the recurrence of cardiac events, with carriers of this genotype 3.4 times less likely to have a recurrent myocardial infarction, heart failure or bypass surgery.
Since Methionine Synthase is dependent on vitamin B12, and the SNP is beneficial, best results will be seen in individuals where there is adequate intake of vitamin B12. Examples of vitamin B12 rich food sources can be viewed below.
Gene-environment interactions and predictors of breast cancer in family-based multi-ethnic groups
Gonzales et al, 2018.