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Licensed Unlicensed Requires Authentication Published by De Gruyter May 12, 2014

Molecular functionality of CYP2C9 polymorphisms and their influence on drug therapy

Yazun Bashir Jarrar and Su-Jun Lee

Abstract

CYP2C9 metabolizes approximately 20% of clinically used drugs, including the narrow therapeutic window drugs warfarin and phenytoin. More than 16,000 variants have been reported in the National Center for Biotechnology Information CYP2C9 database, as well as 58 alleles in the official P450 Nomenclature Committee website. Two single nucleotide polymorphisms represented by the CYP2C9*2 and CYP2C9*3 alleles have been studied extensively. However, in addition to these two alleles, other genetic factors and an individual’s biological characteristics contribute to the overall drug phenotype. A major bottleneck for CYP2C9 pharmacogenomics in clinical field applications is the lack of knowledge regarding the numerous genetic polymorphisms and their molecular functionalities. An unmet gap exists between the ever-growing number of genetic variants and their molecular mechanisms. In the present review, functional changes of all known CYP2C9 protein coding alleles were predicted using in silico analyses and compared with the in vitro and in vivo data. We also summarize functional information from recently reported CYP2C9 variants. Regarding the previously known CYP2C9 variants, we provide an update on the functional information obtained from in vitro and in vitro data.


Corresponding author: Su-Jun Lee, Department of Pharmacology, Pharmacogenomics Research Center, Inje University College of Medicine, Inje University, 633-165 Gaegum-dong, Busanjin-gu, Busan, Republic of Korea, E-mail:

Acknowledgments

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (No. R13-2007-023-00000-0) and by a grant of the National Project for Personalized Genomic Medicine, Ministry for Health and Welfare, Republic of Korea (A111218-PG02).

Conflict of interest statement

Authors’ conflict of interest disclosure: The authors stated that there are no conflicts of interest regarding the publication of this article. Research support played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

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Received: 2014-1-3
Accepted: 2014-4-4
Published Online: 2014-5-12
Published in Print: 2014-12-1

©2014 by De Gruyter

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