Literature DB >> 25001882

Functional characterization of 21 CYP2C19 allelic variants for clopidogrel 2-oxidation.

M Takahashi1, T Saito1, M Ito1, C Tsukada1, Y Katono1, H Hosono1, M Maekawa2, M Shimada2, N Mano2, A Oda3, N Hirasawa1, M Hiratsuka1.   

Abstract

Genetic variations in cytochrome P450 2C19 (CYP2C19) contribute to interindividual variability in the metabolism of therapeutic agents such as clopidogrel. Polymorphisms in CYP2C19 are associated with large interindividual variations in the therapeutic efficacy of clopidogrel. This study evaluated the in vitro oxidation of clopidogrel by 21 CYP2C19 variants harboring amino acid substitutions. These CYP2C19 variants were heterologously expressed in COS-7 cells, and the kinetic parameters of clopidogrel 2-oxidation were estimated. Among the 21 CYP2C19 variants, 12 (that is, CYP2C19.5A, CYP2C19.5B, CYP2C19.6, CYP2C19.8, CYP2C19.9, CYP2C19.10, CYP2C19.14, CYP2C19.16, CYP2C19.19, CYP2C19.22, CYP2C19.24 and CYP2C19.25) showed no or markedly low activity compared with the wild-type protein CYP2C19.1B. This comprehensive in vitro assessment provided insights into the specific metabolic activities of CYP2C19 proteins encoded by variant alleles, and this may to be valuable when interpreting the results of in vivo studies.

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Year:  2014        PMID： 25001882     DOI： 10.1038/tpj.2014.30

Source DB:  PubMed          Journal:  Pharmacogenomics J        ISSN： 1470-269X            Impact factor:   3.550


  18 in total

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7.  Evaluation of the effects of 20 nonsynonymous single nucleotide polymorphisms of CYP2C19 on S-mephenytoin 4'-hydroxylation and omeprazole 5'-hydroxylation.

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Journal:  Clin Pharmacol Ther       Date:  2020-07-22       Impact factor: 6.875

2.  CYP2C19⁎2 Polymorphism in Chilean Patients with In-Stent Restenosis Development and Controls.

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3.  The effects of cytochrome P450 2C19 polymorphism on the metabolism of voriconazole in vitro.

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4.  Next-Generation Sequencing of CYP2C19 in Stent Thrombosis: Implications for Clopidogrel Pharmacogenomics.

Authors:  Joel A Morales-Rosado; Kashish Goel; Lingxin Zhang; Axel Åkerblom; Saurabh Baheti; John L Black; Niclas Eriksson; Lars Wallentin; Stefan James; Robert F Storey; Shaun G Goodman; Gregory D Jenkins; Bruce W Eckloff; Suzette J Bielinski; Hugues Sicotte; Stephen Johnson; Veronique L Roger; Liewei Wang; Richard Weinshilboum; Eric W Klee; Charanjit S Rihal; Naveen L Pereira
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  4 in total

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