What is the most common genetic variation in drug response?

• A. Metabolism of drugs
• B. Drug target site differences
• C. Hypersensitivity potential
• D. Psychosocial responses

Answer: (A)

Variability in drug response most often comes from genetic differences in how drugs are metabolized. The enzymes that handle drug breakdown, especially the cytochrome P450 family, are highly polymorphic. People can be poor, intermediate, extensive, or ultra-rapid metabolizers depending on their variants. This directly changes drug exposure: poor metabolizers may have higher or prolonged drug levels and increased toxicity, while ultra-rapid metabolizers may clear the drug too quickly and have reduced efficacy. That pattern—genetic differences in metabolism driving much of the variability in effects and safety—accounts for the most common genetic influence on drug response. Variants at drug targets or in hypersensitivity genes do matter, but they occur less frequently or impact fewer drugs than metabolic polymorphisms.