Pharmacogenomics and individualized drug therapy

Annu Rev Med. 2006;57:119-37. doi: 10.1146/annurev.med.56.082103.104724.

Abstract

Pharmacogenetics deals with inherited differences in the response to drugs. The best-recognized examples are genetic polymorphisms of drug-metabolizing enzymes, which affect about 30% of all drugs. Loss of function of thiopurine S-methyltransferase (TPMT) results in severe and life-threatening hematopoietic toxicity if patients receive standard doses of mercaptopurine and azathioprine. Gene duplication of cytochrome P4502D6 (CYP2D6), which metabolizes many antidepressants, has been identified as a mechanism of poor response in the treatment of depression. There is also a growing list of genetic polymorphisms in drug targets that have been shown to influence drug response. A major limitation that has heretofore moderated the use of pharmacogenetic testing in the clinical setting is the lack of prospective clinical trials demonstrating that such testing can improve the benefit/risk ratio of drug therapy.

Publication types

  • Review

MeSH terms

  • Biotransformation / genetics*
  • Cytochrome P-450 Enzyme System / genetics*
  • Glucuronosyltransferase / genetics*
  • Humans
  • Methyltransferases / genetics*
  • Polymorphism, Genetic / genetics
  • Receptors, Adrenergic, beta-2 / genetics*
  • Sodium Channels / genetics

Substances

  • Receptors, Adrenergic, beta-2
  • Sodium Channels
  • Cytochrome P-450 Enzyme System
  • Methyltransferases
  • thiopurine methyltransferase
  • UGT1A1 enzyme
  • Glucuronosyltransferase