Influence of CYP2C9 and VKORC1 polymorphisms on warfarin and acenocoumarol in a sample of lebanese people

Maria O. Esmerian, Zahi Mitri, Mohammad Zuheir Habbal, Eddy Geryess, Ghazi Zaatari, Samir Alam, Hadi N. Skouri, Rami A. Mahfouz, Ali Taher, Nathalie K. Zgheib

Research output: Contribution to journalArticle

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Abstract

The authors assessed the impact of CYP2C9*2, CYP2C9*3, and/or VKORC1-1639G>A/1173C>T single-nucleotide polymorphisms on oral anticoagulants in a Lebanese population. This study recruited 231 Lebanese participants on long-term warfarin or acenocoumarol maintenance therapy with an international normalized ratio (INR) monitored at the American University of Beirut Medical Center. CYP2C9 and VKORC1 variant alleles were screened by real-time PCR. Plasma R-and S-warfarin and R-and S-acenocoumarol levels were assayed using high-performance liquid chromatography. The variant allele frequencies of CYP2C9*2, CYP2C9*3, and VKORC1-1639G>A/1173C>T were 15.4%, 7.8%, and 52.4%, respectively. Fifty-five participants were excluded from analysis because of nontherapeutic INR values at recruitment, leaving 43 participants taking warfarin and 133 taking acenocoumarol. There was a significant decrease in the weekly maintenance dose of both drugs with CYP2C9 and VKORC1 variants when compared with wild-type patients. CYP2C9*2 had the least impact on the response to both drugs. The concentrations of R-and S-warfarin in plasma were significantly correlated with CYP2C9 genotypes. For acenocoumarol, time to reach target INR was more prolonged in patients carrying any CYP2C9 variant allele but failed to reach statistical significance because of low numbers of patients. There was no association between allelic variants and bleeding events. This is the first pharmacogenetic study of oral anticoagulants in Arabs. The authors showed that both CYP2C9 and VKORC1 polymorphisms are common in Lebanon and influence warfarin and acenocoumarol dose requirements, with the CYP2C9*2 polymorphism having less effect on acenocoumarol, the most commonly used oral anticoagulant in Lebanon.

Original languageEnglish (US)
Pages (from-to)1418-1428
Number of pages11
JournalJournal of Clinical Pharmacology
Volume51
Issue number10
DOIs
StatePublished - Oct 2011
Externally publishedYes

Fingerprint

Acenocoumarol
Warfarin
International Normalized Ratio
Anticoagulants
Lebanon
Cytochrome P-450 CYP2C9
Alleles
Gene Frequency
Pharmaceutical Preparations
Single Nucleotide Polymorphism
Real-Time Polymerase Chain Reaction

Keywords

  • Anticoagulants
  • CYP2C9
  • pharmacogenetics
  • pharmacokinetics
  • VKORC1

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology

Cite this

Influence of CYP2C9 and VKORC1 polymorphisms on warfarin and acenocoumarol in a sample of lebanese people. / Esmerian, Maria O.; Mitri, Zahi; Habbal, Mohammad Zuheir; Geryess, Eddy; Zaatari, Ghazi; Alam, Samir; Skouri, Hadi N.; Mahfouz, Rami A.; Taher, Ali; Zgheib, Nathalie K.

In: Journal of Clinical Pharmacology, Vol. 51, No. 10, 10.2011, p. 1418-1428.

Research output: Contribution to journalArticle

Esmerian, MO, Mitri, Z, Habbal, MZ, Geryess, E, Zaatari, G, Alam, S, Skouri, HN, Mahfouz, RA, Taher, A & Zgheib, NK 2011, 'Influence of CYP2C9 and VKORC1 polymorphisms on warfarin and acenocoumarol in a sample of lebanese people', Journal of Clinical Pharmacology, vol. 51, no. 10, pp. 1418-1428. https://doi.org/10.1177/0091270010382910
Esmerian, Maria O. ; Mitri, Zahi ; Habbal, Mohammad Zuheir ; Geryess, Eddy ; Zaatari, Ghazi ; Alam, Samir ; Skouri, Hadi N. ; Mahfouz, Rami A. ; Taher, Ali ; Zgheib, Nathalie K. / Influence of CYP2C9 and VKORC1 polymorphisms on warfarin and acenocoumarol in a sample of lebanese people. In: Journal of Clinical Pharmacology. 2011 ; Vol. 51, No. 10. pp. 1418-1428.
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