CYP2D6affecting

CYP2D6 affecting refers to the genetic and non-genetic factors that influence the activity of the cytochrome P450 2D6 enzyme, a key contributor to the metabolism of about a quarter of prescribed medicines. The enzyme is highly polymorphic, and individuals can have a range of metabolic capacities from none to high, which shapes how they process many drugs.

Genetic variation is the main source of interindividual differences in CYP2D6 activity. More than 100 alleles have been identified, leading to poor, intermediate, normal, or ultrarapid metabolizer phenotypes. The combined effect of these alleles determines the overall metabolic capacity, and some people carry multiple copies of functional alleles that accelerate metabolism.

Copy number variation also influences CYP2D6 function. Duplications of functional alleles can give rise to ultrarapid metabolizers, while deletions or nonfunctional alleles can produce poor metabolizers. This genetic architecture creates broad variability in drug exposure among individuals.

Ethnic and population differences exist in CYP2D6 phenotypes. Poor metabolizers are more common in populations of European descent, while ultrarapid metabolizers are more frequent in some North African, Middle Eastern, and Oceanian groups. East Asian populations typically show lower frequencies of ultrarapid metabolism.

Non-genetic factors, including drug interactions, can substantially alter CYP2D6 activity. Many medications inhibit CYP2D6 and slow metabolism (for example, certain antidepressants and antipsychotics), while others have limited inducing effects. Drugs that require CYP2D6 for activation, such as codeine and tramadol, can produce altered analgesia in poor or ultrarapid metabolizers. Clinically, pharmacogenetic testing and guidelines (such as CPIC and DPWG) support drug selection and dosing adjustments for certain CYP2D6 substrates, including considerations for tamoxifen and opioid therapy.