Journal
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS
Volume 573, Issue 1-2, Pages 180-194Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.mrfmmm.2004.07.025
Keywords
pharmacogenetics; pharmacoeconomics
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Several proofs of principle have established that pharmacogenetic testing for mutations altering expression and functions of genes associated with drug disposition and response can decrease the trial-and-error dosing and reduce the risk of adverse drug reactions. These proofs of principle include thiopurine methyltransferase and thiopurine therapy, dihydropyrimidine dehydrogenase/thymidylate synthase and 5-fluorouracil therapy, folate enzyme MTHFR and methotrexate therapy, UGTIA1 and irinotecan therapy and CYP450 2C9 and S-warfarin therapy. These evidences advocate for the prospective identification of mutations associated with drug response, serious adverse reactions and treatment failure. More recent evidence with the HLA basis of hypersensitivity to the retroviral agent abacavir demonstrates the potential of pharmacogenetic testing and its pharmacoeconomic implications. With the convergence of rising drug costs and evidence supporting the clinical benefits of pharmacogenetic testing, it will be important to demonstrate the improved net health outcomes attributed to the additional costs for this testing. (c) 2005 Elsevier B.V. All rights reserved.
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