Clinical Pharmacogenomics: Translating Genetic Variation into Individualized Drug Therapy

Abstract

Clinical pharmacogenomics (PGx) is an emerging component of precision medicine that examines how inherited genetic variation influences an individual's response to medicines. Genetic differences affecting drug-metabolizing enzymes, transporters, receptors, immune pathways and therapeutic targets can contribute to interindividual variability in drug efficacy, toxicity and pharmacokinetics. Integration of pharmacogenomic information into clinical practice can therefore support selection of appropriate medicines, individualized dosing and prevention of avoidable adverse drug reactions. Important gene–drug associations include CYP2C19–clopidogrel, CYP2D6–codeine and antidepressants, CYP2C9/VKORC1–warfarin, TPMT/NUDT15–thiopurines, DPYD–fluoropyrimidines and HLA-B*57:01–abacavir. Clinical implementation is supported by evidence-based resources and guidelines developed by organizations such as the Clinical Pharmacogenetics Implementation Consortium (CPIC), the Dutch Pharmacogenetics Working Group (DPWG), PharmGKB and regulatory agencies. However, challenges involving test accessibility, cost, interpretation, healthcare professional education, electronic health record integration, reimbursement, ethical considerations and population diversity continue to limit widespread implementation. Recent developments in pre-emptive panel testing, clinical decision-support systems and standardized genotype-to-phenotype interpretation are facilitating broader integration of PGx into healthcare. This review discusses the principles, clinical applications, implementation strategies, benefits and limitations of clinical pharmacogenomics and highlights its potential role in individualized and safer pharmacotherapy.