Toggle Main Menu Toggle Search

Open Access padlockePrints

Pharmacogenomics of CYP2C9: Functional and Clinical Considerations

Lookup NU author(s): Professor Ann Daly

Downloads


Licence

This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2018 by the authors. Licensee MDPI, Basel, Switzerland. CYP2C9 is the most abundant CYP2C subfamily enzyme in human liver and the most important contributor from this subfamily to drug metabolism. Polymorphisms resulting in decreased enzyme activity are common in the CYP2C9 gene and this, combined with narrow therapeutic indices for several key drug substrates, results in some important issues relating to drug safety and efficacy.CYP2C9 substrate selectivity is detailed and, based on crystal structures for the enzyme, we describe how CYP2C9 catalyzes these reactions. Factors relevant to clinical response to CYP2C9 substrates including inhibition, induction and genetic polymorphism are discussed in detail. In particular, we consider the issue of ethnic variation in pattern and frequency of genetic polymorphisms and clinical implications. Warfarin is the most well studied CYP2C9 substrate; recent work on use of dosing algorithms that include CYP2C9 genotype to improve patient safety during initiation of warfarin dosing are reviewed and prospects for their clinical implementation considered. Finally, we discuss a novel approach to cataloging the functional capabilities of rare ‘variants of uncertain significance’, which are increasingly detected as more exome and genome sequencing of diverse populations is conducted.


Publication metadata

Author(s): Daly AK, Rettie AE, Fowler DM, Miners JO

Publication type: Review

Publication status: Published

Journal: Journal of Personalized Medicine

Year: 2018

Volume: 8

Issue: 1

Online publication date: 28/12/2017

Acceptance date: 20/12/2017

ISSN (print): 2075-4426

Publisher: MDPI AG

URL: https://doi.org/10.3390/jpm8010001

DOI: 10.3390/jpm8010001


Actions

Find at Newcastle University icon    Link to this publication


Share