What is the Origin of COMT Val158Met Polymorphism?

The COMT gene and its resulting enzyme are integral to the neuroendocrine system, specifically in managing neurotransmitter and hormone clearance. The identification of this common variation arose from molecular genetic studies investigating individual differences in pain sensitivity, stress response, and susceptibility to certain psychiatric conditions. The nomenclature, Val158Met, precisely indicates the amino acid substitution and its location within the protein structure.

What is the Mechanism of COMT Val158Met Polymorphism?

The Val allele produces a COMT enzyme that is approximately three to four times more active than the Met allele enzyme, leading to a much faster breakdown of catecholamines and catechol estrogens. Conversely, the Met allele results in a less efficient enzyme, leading to higher and more sustained levels of these neurochemicals and hormones in the prefrontal cortex and other tissues. This difference in enzyme activity influences cognitive function, emotional regulation, and the metabolic clearance of estrogen metabolites, linking this polymorphism to variations in hormonal health and stress resilience.

COMT Val158Met Polymorphism ∞ Area

COMT Val158Met Polymorphism

Meaning

The COMT Val158Met Polymorphism is a specific, common genetic variation (single nucleotide polymorphism or SNP) within the catechol-O-methyltransferase (COMT) gene, resulting in an amino acid change from Valine (Val) to Methionine (Met) at position 158 of the enzyme. This particular genetic variant significantly impacts the efficiency of the COMT enzyme, which is responsible for the metabolic breakdown of catecholamines, including dopamine, norepinephrine, and epinephrine, as well as certain catechol estrogens. Individuals can be homozygous for Val/Val, heterozygous for Val/Met, or homozygous for Met/Met.

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HRTioJuly 29, 2025

COMT Val158Met Polymorphism

Meaning

Origin

Mechanism

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