pharmacogenetics

Pharmacogenetics is a field of study examining how inherited genetic variation influences individual responses to medications. The aim is to understand why people respond differently to the same drug and to tailor therapy to maximize efficacy and minimize adverse effects. Historically focused on single genes, pharmacogenetics is a component of the broader field of pharmacogenomics, which uses genome-wide data to predict drug response.

Genetic variations in drug-metabolizing enzymes (notable CYP450s), drug transporters, and drug targets contribute to variability. For example, CYP2D6, CYP2C9, and CYP2C19 genetic variants affect metabolism of many drugs, producing phenotypes such as poor, intermediate, extensive, or ultra-rapid metabolizers. TPMT variants influence thiopurine toxicity. VKORC1 and CYP2C9 variants influence warfarin dose requirements. Clopidogrel efficacy is reduced in CYP2C19 loss-of-function carriers. HLA alleles, such as HLA-B*15:02 and HLA-B*57:01, are associated with adverse reactions to certain drugs (carbamazepine-induced SJS in some populations; abacavir hypersensitivity).

Clinical use and guidelines: Pharmacogenetic testing may guide drug selection and dosing, with guidelines from CPIC and others, and is increasingly integrated into electronic health records and decision support. Testing can be pre-emptive or targeted when a drug is prescribed. Benefits include improved efficacy, reduced adverse drug reactions, and faster optimization of therapy, though the magnitude of benefit varies by drug and population.

Limitations and considerations: Genetic effect sizes are often modest, environmental factors and comedications influence response, and many variants are population-specific. Cost, access, and ethical issues regarding privacy and consent also affect implementation.