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Clinically Relevant Genetic Variations in Drug Metabolizing Enzymes

[ Vol. 12 , Issue. 5 ]

Author(s):

Navin Pinto and M. Eileen Dolan   Pages 487 - 497 ( 11 )

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

Affiliation:

University of Chicago 900 E.57th Street, 5th Floor Chicago, IL 60637 USA.



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