Abstract
In the field of pharmacogenetics, we currently have a few markers to guide physicians as to the best course of therapy for patients. For the most part, these genetic variants are within a drug metabolizing enzyme that has a large effect on the degree or rate at which a drug is converted to its metabolites. For many drugs, response and toxicity are multi-genic traits and understanding relationships between a patients genetic variation in drug metabolizing enzymes and the efficacy and/or toxicity of a medication offers the potential to optimize therapies. This review will focus on variants in drug metabolizing enzymes with predictable and relatively large impacts on drug efficacy and/or toxicity; some of these drug/gene variant pairs have impacted drug labels by the United States Food and Drug Administration. The challenges in identifying genetic markers and implementing clinical changes based on known markers will be discussed. In addition, the impact of next generation sequencing in identifying rare variants will be addressed.
Keywords: Adverse drug reactions, Cytochrome P450, drug metabolizing enzymes, pharmacogenetics, pharmacogenomics, single nucleotide polymorphisms, glucuronidation, acetylation, phase II conjugation reactions, lipophilic, sulfation, hemoproteins
Current Drug Metabolism
Title: Clinically Relevant Genetic Variations in Drug Metabolizing Enzymes
Volume: 12 Issue: 5
Author(s): Navin Pinto and M. Eileen Dolan
Affiliation:
Keywords: Adverse drug reactions, Cytochrome P450, drug metabolizing enzymes, pharmacogenetics, pharmacogenomics, single nucleotide polymorphisms, glucuronidation, acetylation, phase II conjugation reactions, lipophilic, sulfation, hemoproteins
Abstract: In the field of pharmacogenetics, we currently have a few markers to guide physicians as to the best course of therapy for patients. For the most part, these genetic variants are within a drug metabolizing enzyme that has a large effect on the degree or rate at which a drug is converted to its metabolites. For many drugs, response and toxicity are multi-genic traits and understanding relationships between a patients genetic variation in drug metabolizing enzymes and the efficacy and/or toxicity of a medication offers the potential to optimize therapies. This review will focus on variants in drug metabolizing enzymes with predictable and relatively large impacts on drug efficacy and/or toxicity; some of these drug/gene variant pairs have impacted drug labels by the United States Food and Drug Administration. The challenges in identifying genetic markers and implementing clinical changes based on known markers will be discussed. In addition, the impact of next generation sequencing in identifying rare variants will be addressed.
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Cite this article as:
Pinto Navin and Eileen Dolan M., Clinically Relevant Genetic Variations in Drug Metabolizing Enzymes, Current Drug Metabolism 2011; 12 (5) . https://dx.doi.org/10.2174/138920011795495321
DOI https://dx.doi.org/10.2174/138920011795495321 |
Print ISSN 1389-2002 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5453 |
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