Pharmacogenetics: has it reached the clinic?

Genetic variation in drug-metabolizing enzymes contributes to the variability in drug responses seen in humans. Information in the area is expanding rapidly, and the clinical significance of many of the polymorphisms is only now being elucidated. It is clear that polymorphism frequency varies markedly by race and ethnicity, but major differences by sex have not been reported. Screening for genetic variation in most drug-metabolizing enzymes is not recommended; the very important exception is the need to determine the thiopurine transferase activity of patients who may receive thiopurines (e.g., 6-mercaptopurine and azathioprine) because clinically life-threatening complications or decreased efficacy is strongly related to the genetically determined activity of this enzyme.