The methylation cycle runs around the clock in every cell, supporting gene regulation, neurotransmitter synthesis, homocysteine clearance, and DNA repair.
MTHFR, the enzyme at the center of folate and one-carbon metabolism, and its common C677T and A1298C variants.
The Biology
One-carbon metabolism, the network of reactions that moves methyl groups through the cell, supports epigenetic regulation, amino acid processing, and the synthesis of neurotransmitters including dopamine, serotonin, and norepinephrine. MTHFR makes the form of folate this cycle uses. Reduced MTHFR activity is associated with higher homocysteine, especially when folate intake is low.
What Varia Analyzes
MTHFR C677T (rs1801133) and A1298C (rs1801131), the common variants in the gene. In the studies the catalog cites, C677T heterozygotes have about 65 percent of typical MTHFR enzyme activity and homozygotes about 30 percent; A1298C has a smaller effect on its own.
Why It Matters
Carrying one copy of each variant, called compound heterozygosity, is the combination the catalog's sources describe as most significant for A1298C. These variants describe enzyme activity, not a diagnosis; homocysteine and folate levels are measured with a blood test.
Not in Varia's Catalog
Other methylation and absorption variants often discussed are not in the catalog: MTR A2756G (rs1805087), MTRR A66G (rs1801394), CBS (rs234706), BHMT (rs3733890), and FUT2 secretor status (rs601338). Varia does not read these from your file, so a scan reports nothing about them either way.
Key Sources
- Frosst P, et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet. 1995.
- van der Put NM, et al. A second common mutation in the methylenetetrahydrofolate reductase gene: an additional risk factor for neural-tube defects. Am J Hum Genet. 1998.
- Blom HJ, Smulders Y. Overview of homocysteine and folate metabolism with special references to cardiovascular disease and neural tube defects. J Inherit Metab Dis. 2011.