Pharmacogenomics

Pharmacogenomics studies how genetic variation — primarily in drug-metabolizing enzymes, transporters, and drug targets — influences individual drug response in terms of efficacy and toxicity. CYP2C9 and VKORC1 variants are the canonical example for warfarin dosing: poor metabolizers at CYP2C9 combined with VKORC1 low-expression haplotypes require markedly lower doses to achieve therapeutic anticoagulation, and dosing algorithms incorporating genotype reduce bleeding events. For statins, a non-synonymous variant in SLCO1B1 (rs4149056, Val174Ala) reduces hepatic uptake of simvastatin and atorvastatin, raising plasma drug levels and increasing myopathy risk several-fold in CC homozygotes. Pharmacogenomics is particularly relevant to older adults with polypharmacy because drug-drug-gene interactions compound with age-related changes in kidney and liver function; clinical implementation through pre-emptive panel genotyping is expanding, with CPIC guidelines providing evidence-based dose recommendations for over 40 drug-gene pairs.