Polymorphism of human cytochrome P450 2C9 and the functional relevance

Zhou, S, Zhou, Z and Huang, M 2009, 'Polymorphism of human cytochrome P450 2C9 and the functional relevance', Toxicology, pp. 1-24.


Document type: Journal Article
Collection: Journal Articles

Title Polymorphism of human cytochrome P450 2C9 and the functional relevance
Author(s) Zhou, S
Zhou, Z
Huang, M
Year 2009
Journal name Toxicology
Start page 1
End page 24
Total pages 24
Publisher Elsevier BV
Abstract Human cytochrome P450 2C9 (CYP2C9) accounts for ~20% of hepatic total CYP content and metabolizes ~15% clinical drugs such as phenytoin, S-warfarin, tolbutamide, losartan, and many nonsteroidal anti-inflammatory agents (NSAIDs). CYP2C9 is highly polymorphic, with at least 33 variants of CYP2C9 (*1B through *34) being identified so far. CYP2C9*2 is frequent among Caucasians with ~1% of the population being homozygous carriers and 22% are heterozygous. The corresponding figures for the CYP2C9*3 allele are 0.4% and 15%, respectively. There are a number of clinical studies addressing the impact of CYP2C9 polymorphisms on the clearance and/or therapeutic response of therapeutic drugs. These studies have highlighted the importance of the CYP2C9*2 and *3 alleles as a determining factor for drug clearance and drug response. The CYP2C9 polymorphisms are relevant for the efficacy and adverse effects of numerous NSAIDs, sulfonylurea antidiabetic drugs and, most critically, oral anticoagulants belonging to the class of vitamin K epoxide reductase inhibitors. Warfarin has served as a practical example of how pharmacogenetics can be utilized to achieve maximum efficacy and minimum toxicity. For many of these drugs, a clear gene-dose and gene-effect relationship has been observed in patients. In this regard, CYP2C9 alleles can be considered as a useful biomarker in monitoring drug response and adverse effects. Genetic testing ofCYP2C9 is expected to play a role in predicting drug clearance and conducting individualized pharmacotherapy. However, prospective clinical studies with large samples are warranted to establish gene-dose and gene-effect relationships for CYP2C9 and its substrate drugs.
Subject Enzymes
Keyword(s) CYP2C9
SNP
enzyme activity
ethnic
clearance
adverse effect
adverse effect
DOI - identifier 10.1016/j.tox.2009.08.013
Copyright notice © 2009 Elsevier Ireland Ltd.
ISSN 18793185
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