DNA Health > Methylation

Methionine Synthase


Allele Frequency in Population

The 1000 Genomes Project Database reports a global frequency of 36% for the G allele (NIH).

Gene and SNP Summary

The MTRR gene encodes the methionine synthase reductase enzyme, which is responsible for the methylation of methionine synthase, and therefore helps keep homocysteine at non-toxic levels. The G allele is associated with altered enzyme function and has been linked to increased risk for higher homocysteine levels, cardiovascular diseases and neural tube defects (NTD), especially when vitamin B12 is insufficient.




MTRR Gene Detail

MTRR encodes a member of the ferredoxin-NADP(+) reductase (FNR) family of electron transferases. This enzyme is responsible for the synthesis of methionine by regenerating methionine synthase to a functional state, and is thus important for folate metabolism and cellular methylation.




The MTRR A66G SNP results in an amino acid change from Isoleucine to Methionine at position 22 of the protein. This functional change is associated with a decrease in the enzyme activity and therefore raised homocysteine levels. The G allele, specifically the GG genotype, has been linked with numerous chronic diseases of lifestyle as well as risk for male infertility, NTDs and cleft clip.

In a meta-analysis by Yadav et al., the G allele was significantly associated with risk of NTDs and, in a recent case-control study of NTDs by Cai et al, the MTRR G allele was again significantly higher in cases than in controls. Folate deficiency was also a key factor linking SNPs with risk of NTDs.

Du et al found that homocysteine levels in at risk G allele carriers can be controlled with adequate folate intake. Similarly, it was demonstrated that genomic stability, and moderating risk of breast cancer, can be achieved in MTRR G allele carriers when vitamin B6 levels are adequate. Zhi et al found another gene-environment interaction where risk of diabetes is modulated by the MTRR AG and GG genotype and being overweight/obese.



In G allele carriers, it should be noted that risks can be mitigated by achieving adequate levels of folate, and vitamin B6. Examples of vitamin B6 and folate rich food sources can be viewed below. Weight management is also imperative to control risk for diabetes in G allele carriers.





The Role of Genetic Polymorphisms as Related to One-Carbon Metabolism, Vitamin B6, and Gene–Nutrient Interactions in Maintaining Genomic Stability and Cell Viability in Chinese Breast Cancer Patients

Wu et al, 2016.