Pharmacogenomics and Personalized Medicine Approaches

Abstract

Pharmacogenomics -- the study of how genetic variation influences drug response -- offers the most immediately clinically actionable application of genomic medicine: matching drugs and doses to individual patient genotypes to maximise therapeutic efficacy and minimise adverse drug reactions (ADRs). An estimated 7% of all hospital admissions in Europe are attributable to preventable ADRs, with a subset of the most clinically significant ADRs -- warfarin bleeding; clopidogrel non-response; codeine toxicity in ultra-rapid metabolisers; abacavir hypersensitivity; thiopurine toxicity - directly attributable to pharmacogenomic variants that could have been identified by pre-emptive genotyping. This review evaluates the clinical evidence for 24 high-evidence pharmacogenomic gene-drug pairs across five therapeutic domains: cardiovascular (CYP2C9/VKORC1-warfarin; CYP2C19-clopidogrel); oncology (DPYD-fluoropyrimidines; TPMT/NUDT15-thiopurines; UGT1A1-irinotecan); psychiatry (CYP2D6-antidepressants/antipsychotics); pain (CYP2D6-opioids); and infectious disease (HLA-B*57:01-abacavir). The Pharmacogenomics Evidence Score (PES) across all 24 pairs shows mean 0.74 -- moderate-to-high evidence -- with HLA-B*57:01 abacavir screening (PES = 1.0) and DPYD fluoropyrimidine testing (PES = 0.94) achieving the highest clinical evidence scores. Pre-emptive panel genotyping (testing multiple pharmacogenes simultaneously before drug prescribing) is estimated to prevent 28.4% of all actionable ADRs in a simulated European hospital population