What is the Origin of CYP2D6 Polymorphism?

The term is a combination of the enzyme family name, Cytochrome P450, and 'polymorphism,' from the Greek meaning 'many shapes,' referring to the multiple allelic variants of the gene. The clinical significance of these genetic variations was recognized through observations of highly variable patient responses to standard drug doses, leading to the field of pharmacogenetics. This discovery is pivotal in tailoring hormonal therapies and other psychotropic medications.

What is the Mechanism of CYP2D6 Polymorphism?

The specific genetic variant dictates the enzyme's functional capacity, directly influencing the rate at which it metabolizes its substrate drugs, including certain antidepressants, opioids, and tamoxifen, which is relevant in hormone-sensitive cancers. Poor metabolizers break down the drug slowly, leading to high plasma concentrations and potential toxicity, while ultrarapid metabolizers clear the drug too quickly, resulting in sub-therapeutic levels and treatment failure. Genotyping for this polymorphism allows clinicians to anticipate and adjust dosing to ensure efficacy and safety.

CYP2D6 Polymorphism

Meaning

A common variation, or polymorphism, in the gene that codes for the Cytochrome P450 2D6 enzyme, a critical enzyme primarily found in the liver responsible for metabolizing approximately 25% of all clinically used drugs. These genetic variations result in individuals being categorized as ultrarapid, extensive, intermediate, or poor metabolizers, profoundly affecting how they process certain medications. Understanding a patient’s CYP2D6 status is essential for personalized medicine and optimizing therapeutic drug dosing.