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Pharmacogenetics of the cytochromes P450: Selected pharmacological and toxicological aspects

Lookup NU author(s): Professor Ann DalyORCiD


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© 2022 Elsevier Inc.With the availability of detailed genomic data on all 57 human cytochrome P450 genes, it is clear that there is substantial variability in gene product activity with functionally significant polymorphisms reported across almost all isoforms. This article is concerned mainly with 13 P450 isoforms of particular relevance to xenobiotic metabolism. After brief review of the extent of polymorphism in each, the relevance of selected P450 isoforms to both adverse drug reaction and disease susceptibility is considered in detail. Bleeding due to warfarin and other coumarin anticoagulants is considered as an example of a type A reaction with idiosyncratic adverse drug reactions affecting the liver and skin as type B. It is clear that CYP2C9 variants contribute significantly to warfarin dose requirement and also risk of bleeding, with a minor contribution from CYP4F2. In the case of idiosyncratic adverse drug reactions, CYP2B6 variants appear relevant to both liver and skin reactions to several drugs with CYP2C9 variants also relevant to phenytoin-related skin rash. The relevance of P450 genotype to disease susceptibility is also considered but detailed genetic studies now suggest that CYP2A6 is the only P450 relevant to risk of lung cancer with alleles associated with low or absent activity clearly protective against disease. Other cytochrome P450 genotypes are generally not predictors for risk of cancer or other complex disease development.

Publication metadata

Author(s): Daly AK

Publication type: Book Chapter

Publication status: Published

Book Title: Advances in Pharmacology

Year: 2022

Volume: 95

Pages: 49-72

Online publication date: 20/07/2022

Acceptance date: 02/04/2018

Publisher: Academic Press Inc.


DOI: 10.1016/bs.apha.2022.05.001

Library holdings: Search Newcastle University Library for this item

ISBN: 9780323911092