What is the Origin of COMT Rs4680?

This genetic variant is a product of natural human evolution, representing a minor alteration in the DNA sequence that has become common across populations. The term itself is derived from the official reference SNP identification number, rs4680, assigned by the NCBI database to catalog the specific G to A base pair substitution. Its clinical significance in endocrinology and neurobiology emerged from pharmacogenetic studies investigating individual variations in drug and hormone metabolism.

What is the Mechanism of COMT Rs4680?

The mechanism is a substitution of the amino acid Valine (Val) for Methionine (Met) at codon 158 of the COMT enzyme, which significantly alters the enzyme's thermal stability and subsequent activity. The Met/Met genotype results in a three-to-four-fold lower enzyme activity, leading to slower breakdown of catecholamines and catechol estrogens. Conversely, the Val/Val genotype exhibits high activity, resulting in rapid degradation of these compounds; this difference in metabolic speed dictates an individual's unique neuroendocrine response and hormonal clearance profile.

COMT Rs4680 ∞ Area

COMT Rs4680

Meaning

COMT Rs4680 identifies a specific Single Nucleotide Polymorphism, or SNP, located within the catechol-O-methyltransferase gene, resulting in a common functional variation known as Val158Met. This genetic polymorphism directly impacts the efficiency of the COMT enzyme, which is critical for metabolizing catecholamines like dopamine and norepinephrine, as well as catechol estrogens. The resulting enzyme activity differences can influence mood, cognitive function, and the detoxification pathway for certain estrogen metabolites.