Functional Characterization of Human CYP2C9 Allelic Variants in COS-7 Cells.

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Du H, Wei Z, Yan Y, Xiong Y, Zhang X, Shen L, Ruan Y, Wu X, Xu Q, He L, Qin S

Functional Characterization of Human CYP2C9 Allelic Variants in COS-7 Cells.

Front Pharmacol. 2016 Apr 25;7:98. doi: 10.3389/fphar.2016.00098. eCollection 2016.

PubMed ID

27199745 [ View in PubMed

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Abstract

Variability in activity of CYP2C9, which is involved in the metabolism of approximately 15% of current therapeutic drugs, is an important contributor to interindividual differences in drug response. To evaluate the functional alternations of CYP2C9(*)2, CYP2C9(*)3, CYP2C9(*)8, CYP2C9(*)11 and CYP2C9(*)31, identified in our previous study in Chinese Han population, allelic variants as well as the wild-type CYP2C9 were transiently expressed in COS-7 cells. Kinetic parameters (Km, Vmax, and Clint) for S-warfarin 7-hydroxylation by these recombinant CYP2C9s were determined. Relative to CYP2C9.1, recombinant CYP2C9.3 and CYP2C9.11 exhibited significantly higher Km values, and all allelic variants showed significantly decreased Vmax and Clint values. Among all allelic variants, catalytic activity of CYP2C9.3 and CYP2C9.11 reduced the most (8.2% and 9.8% of Clint ratio, respectively; P < 0.001). These findings should be useful for predicting the phenotype profiles of CYP2C9 in Chinese Han population, comparing the functional results of these alleles accurately, and finally optimizing pharmacotherapy of drug treatment.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Omeprazole	Cytochrome P450 2C9	Protein	Humans	Unknown	Substrate	Details
Piroxicam	Cytochrome P450 2C9	Protein	Humans	Unknown	Substrate	Details
Progesterone	Cytochrome P450 2C9	Protein	Humans	Unknown	Substrate Inhibitor	Details