Pharmacogenomics: catechol O-methyltransferase to thiopurine S-methyltransferase.

Research output: Contribution to journalReview articlepeer-review

49 Scopus citations

Abstract

1. Pharmacogenomics is the study of the role of inheritance in variation in the drug response phenotype-a phenotype that can vary from adverse drug reactions at one end of the spectrum to lack of therapeutic efficacy at the other. 2. The thiopurine S-methyltransferase (TPMT) genetic polymorphism represents one of the best characterized and most clinically relevant examples of pharmacogenomics. This polymorphism has also served as a valuable "model system" for studies of the ways in which variation in DNA sequence might influence function. 3. The discovery and characterization of the TPMT polymorphism grew directly out of pharmacogenomic studies of catechol O-methyltransferase (COMT), an enzyme discovered by Julius (Julie) Axelrod and his coworkers. 4. This review will outline the process by which common, functionally significant genetic polymorphisms for both COMT and TPMT were discovered and will use these two methyltransferase enzymes to illustrate general principles of pharmacogenomic research-both basic mechanistic and clinical translational research-principles that have been applied to a series of genes encoding methyltransferase enzymes.

Original languageEnglish (US)
Pages (from-to)539-561
Number of pages23
JournalCellular and molecular neurobiology
Volume26
Issue number4-6
DOIs
StatePublished - 2006

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

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