pharmacogenetic

Pharmacogenetics is the scientific discipline that studies how genetic variation influences an individual’s response to drugs. By linking specific DNA polymorphisms to differences in drug metabolism, efficacy, and risk of adverse effects, the field seeks to personalize medication regimens to improve therapeutic outcomes and reduce toxicity.

The origins of pharmacogenetics trace back to observations in the mid‑20th century that certain populations experienced distinct drug reactions, such as the severe toxicity of the anti‑malaria drug primaquine in people with glucose‑6‑phosphate dehydrogenase deficiency. The discovery of cytochrome P450 enzymes and their genetic variants in the 1970s provided a molecular basis for many of these differences, leading to the term “pharmacogenomics” for broader genome‑wide investigations.

Key mechanisms involve variations in genes encoding drug‑metabolizing enzymes (e.g., CYP2D6, CYP2C19), drug targets (e.g., VKORC1 for warfarin), and transport proteins (e.g., ABCB1). These polymorphisms can result in poor, intermediate, extensive, or ultra‑rapid metabolism, which in turn affects drug plasma concentrations and clinical response.

Clinical applications are expanding. Genotype‑guided dosing of anticoagulants, antidepressants, and thiopurines is now incorporated into guidelines from agencies such as the Clinical Pharmacogenetics Implementation Consortium. Oncology has embraced pharmacogenetics through companion diagnostics that match tumor genetic profiles with targeted therapies.

Challenges remain, including the limited representation of diverse ethnic groups in genetic databases, integration of genotyping into routine care, and reimbursement issues. Ongoing research aims to refine predictive models, develop point‑of‑care testing, and incorporate polygenic risk scores, positioning pharmacogenetics as a central component of precision medicine.