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. 2014 Aug;24(8):381-6.
doi: 10.1097/FPC.0000000000000068.

The influence of the CYP2C19*10 allele on clopidogrel activation and CYP2C19*2 genotyping

Taimour Y Langaee  1 , Hao-Jie Zhu, Xinwen Wang, Nihal El Rouby, John S Markowitz, Joyce A Goldstein, Julie A Johnson
Affiliations

The influence of the CYP2C19*10 allele on clopidogrel activation and CYP2C19*2 genotyping

Taimour Y Langaee et al. Pharmacogenet Genomics. 2014 Aug.

Erratum in

  • Pharmacogenet Genomics. 2014 Dec;24(12):622

Abstract

Background/objectives: The polymorphic hepatic enzyme CYP2C19 catalyzes the metabolism of clinically important drugs such as clopidogrel, proton-pump inhibitors, and others and clinical pharmacogenetic testing for clopidogrel is increasingly common. The CYP2C19*10 single-nucleotide polymorphism (SNP) is located 1 bp upstream the CYP2C19*2 SNP. Despite the low frequency of the CYP2C19*10 allele, its impact on metabolism of CYP2C19 substrates and CYP2C19*2 genotyping makes it an important SNP to consider for pharmacogenetic testing of CYP2C19. However, the effect of the CYP2C19*10 allele on clopidogrel metabolism has not been explored to date.

Methods: We measured the enzymatic activity of the CYP2C19.10 protein against clopidogrel. DNA samples from two clinical studies were genotyped for CYP2C19*2 and *10 by pyrosequencing genotyping method.

Results: The catalytic activity of CYP2C19.10 in the biotransformation of clopidogrel and 2-oxo-clopidogrel was significantly decreased relative to the wild-type CYP2C19.1B. We also reported that the CYP2C19*10 SNP interferes with the CYP2C19*2 TaqMan genotyping assay, resulting in miscalling of CYP2C19*10/*2 as CYP2C19*2/*2.

Conclusions: Our data provide evidence that CYP2C19.10 variant partially metabolizes clopidogrel and 2-oxo-clopidogrel, and the presence of CYP2C19*10 allele affects the CY2C19*2 TaqMan genotyping assay and results in misclassification of CYP2C19*10/*2 as CYP2C19*2/*2.

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Conflict of interest statement

Conflict of Interest

There are no conflicts of interest declared.

Figures

Figure 1
Figure 1
Predicted histogram and pyrogram along with genotype call for an individual with CYP2C19*10 (C/T) and CYP2C19*2 (G/A) genotype are shown. The order of nucleotide dispensation is located at the bottom of histogram and pyrogram.
Figure 2
Figure 2
Kinetic analysis of catalytic activity of CYP2C19.1B (wild type) and CYP2C19.10 proteins on the metabolism of omeprazole (A), S-mephenytoin (B), 2-oxo-clopidogrel (C), and clopidogrel (D). Enzymatic activity was determined by the measurements of respective metabolites as indicated in the Y axis title of each figure. Values are means ± SD of two independent experiments.
See this image and copyright information in PMC

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