pharmacogenotypes

Pharmacogenotype refers to the genetic makeup of an individual that affects their response to medications. It concerns variants in genes encoding drug-metabolizing enzymes, drug transporters, drug targets, and components of drug response pathways. These genetic differences can influence pharmacokinetics (how the body processes a drug) and pharmacodynamics (how a drug affects the body), leading to variability in efficacy and risk of adverse effects among individuals.

Many pharmacogenotypes involve cytochrome P450 enzymes (CYP2D6, CYP2C9, CYP2C19, CYP3A5) that metabolize many drugs. Others include TPMT and NUDT15 for thiopurines; VKORC1 and CYP2C9 for warfarin; and HLA alleles (such as HLA-B*15:02 and HLA-B*57:01) linked to drug hypersensitivity reactions.

In clinical practice, pharmacogenetic testing can guide drug choice and dosing. Professional guidelines from groups such as CPIC translate genotype results into actionable recommendations, for example adjusting warfarin dose based on VKORC1/CYP2C9 genotype or assessing clopidogrel efficacy via CYP2C19 status.

Limitations include incomplete penetrance, environmental factors, drug interactions, and polygenic influences. A genotype does not always predict phenotype, and testing may not be available or affordable for all patients. Allele frequencies vary among populations, which can affect the utility of pharmacogenetic testing in different ethnic groups.

The field continues to grow with efforts to integrate pharmacogenotypes into electronic health records and dosing algorithms, expand the catalogue of clinically relevant gene–drug pairs, and improve patient access to testing.