COMT genetics (catechol-O-methyltransferase)

COMT stands for catechol-O-methyltransferase, an enzyme that inactivates messengers such as dopamine, noradrenaline and adrenaline as well as certain breakdown products of oestrogens. The COMT gene is examined for a common variant that changes how fast the enzyme works; studies focus above all on the Val158Met variant (rs4680). Which variant was determined is stated in the report. The sample is EDTA blood; as a genetic test, written consent is required. COMT is part of the “Depression genetics” analysis together with TPH2, the serotonin transporter, the 5-HT2A receptor and MAO-A. The result stays the same for life.

What COMT does in the body

COMT transfers a methyl group from S-adenosylmethionine (SAMe) to substances with a catechol structure. This inactivates dopamine, noradrenaline and adrenaline so that they can be broken down further and excreted; the 2- and 4-hydroxyoestrogens are turned into the less reactive methoxyoestrogens. The enzyme exists in a soluble form, mainly in the liver, kidneys and gut, and in a membrane-bound form that predominates in the brain. The frontal brain (prefrontal cortex) has only a few dopamine transporters to take dopamine back into the nerve cells – there, COMT therefore has a particularly strong say in how long dopamine acts. The enzyme needs magnesium as a cofactor; its by-product is S-adenosylhomocysteine, the precursor of homocysteine.

What does the COMT Val158Met variant mean for metabolism?

In Val158Met, the amino acid valine is replaced by methionine at position 158 of the membrane-bound form (position 108 of the soluble form). The Met form is less stable at body temperature: in laboratory studies, enzyme activity with two Met copies was clearly lower than with two Val copies, with mixed carriers (Val/Met) in between. Less activity means that dopamine and noradrenaline are broken down more slowly, especially in the frontal brain, and can act for longer; with Val/Val they are inactivated faster. The methylation of catechol oestrogens can shift accordingly. In European populations both forms are about equally common; in East Asian and African populations the Met form is less frequent.

What can be read from the COMT genotype?

Links between the COMT genotype and stress processing, pain perception, memory or mood have been examined in many studies. The results are inconsistent, the effects found are mostly small, and many findings could not be confirmed in large studies. Popular labels such as “warrior” or “worrier” are therefore not supported by evidence. The genotype describes a property of the enzyme – how much dopamine or noradrenaline is actually present also depends on the production and reuptake of these messengers, on the supply of SAMe and magnesium and on other genes. The messengers themselves are measured in the neurotransmitter analyses.

The interpretation is given in your report.