molecular panel
Genotyping — MTHFR + COMT
Two common variants in genes that sit on opposite ends of the methylation cycle — one in the enzyme that produces the cell's methyl supply, one in an enzyme that spends it.
Specification
- Specimen
- Whole blood or buccal swab
- Collection
- Tube
- LAV
Background
Methylation is the transfer of a single carbon atom onto another molecule, and the cell does it constantly: building and silencing DNA, making and clearing neurotransmitters, processing hormones, producing creatine and phospholipids.
Almost all of it runs through one donor, S-adenosylmethionine. SAM gives up its methyl group, becomes homocysteine, and is regenerated through a cycle that depends on folate and vitamin B12. MTHFR and COMT sit at opposite ends of that cycle — one helps produce the methyl supply, the other spends it.
MTHFR encodes methylenetetrahydrofolate reductase, which converts 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate — the circulating form of folate. That molecule donates its methyl group to homocysteine, regenerating methionine and, from it, SAM. Two variants are commonly reported. The c.677C>T substitution replaces alanine with valine, which makes the enzyme less thermostable and lowers its activity; c.1298A>C is the second.
COMT encodes catechol-O-methyltransferase, which spends SAM methylating catechol compounds — the catecholamine neurotransmitters dopamine, norepinephrine and epinephrine, and the catechol estrogens. The commonly reported variant, Val158Met, substitutes methionine for valine; the methionine form is less thermostable at body temperature and has substantially lower activity.