Epidemiological Evidence of Drug Metabolism Gene Polymorphisms and Individual Differences in Drug Response

Abstract

Interindividual variability in drug response poses a significant challenge in clinical practice, leading to treatment failure or adverse drug reactions (ADRs). A substantial portion of this variability is driven by genetic polymorphisms in key pharmacogenes. This review aims to synthesize the robust evidence and clinical guidelines for major gene-drug pairs and to discuss the critical evidence gaps hindering the equitable global implementation of pharmacogenomics. We conducted a comprehensive review of systematic reviews, meta-analyses, and clinical guidelines from consortia like the Clinical Pharmacogenetics Implementation Consortium (CPIC) for key gene-drug interactions, including CYP2C19-clopidogrel, CYP2C9/VKORC1-warfarin, SLCO1B1-statins, and SLC22A1-metformin. Furthermore, we examined the issue of population bias in genetic research and the need for real-world evidence. Strong evidence confirms that genetic variants significantly alter the efficacy and toxicity of numerous drugs. CPIC guidelines provide actionable recommendations for genotype-guided therapy, such as alternative antiplatelet agents for CYP2C19 poor metabolizers and dose adjustments for warfarin and statins.