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

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

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

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 onmetabolism 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-oxoclopidogrel, 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.

Original languageEnglish
Pages (from-to)381-386
Number of pages6
JournalPharmacogenetics and Genomics
Volume24
Issue number8
DOIs
StatePublished - Aug 2014
Externally publishedYes

Keywords

  • CYP2C19*10
  • clopidogrel
  • genotyping
  • pharmacogenetic
  • pharmacokinetic

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