Tags

Type your tag names separated by a space and hit enter

Influence of CYP2C9 and VKORC1 polymorphisms on warfarin and acenocoumarol in a sample of Lebanese people.
J Clin Pharmacol. 2011 Oct; 51(10):1418-28.JC

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.

Authors+Show Affiliations

Pharmacology & Therapeutics, Faculty of Medicine, American University of Beirut, Riad El Solh, Beirut 1107 2020, Lebanon.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21148049

Citation

Esmerian, Maria O., et al. "Influence of CYP2C9 and VKORC1 Polymorphisms On Warfarin and Acenocoumarol in a Sample of Lebanese People." Journal of Clinical Pharmacology, vol. 51, no. 10, 2011, pp. 1418-28.
Esmerian MO, Mitri Z, Habbal MZ, et al. Influence of CYP2C9 and VKORC1 polymorphisms on warfarin and acenocoumarol in a sample of Lebanese people. J Clin Pharmacol. 2011;51(10):1418-28.
Esmerian, M. O., Mitri, Z., Habbal, M. Z., Geryess, E., Zaatari, G., Alam, S., Skouri, H. N., Mahfouz, R. A., Taher, A., & Zgheib, N. K. (2011). Influence of CYP2C9 and VKORC1 polymorphisms on warfarin and acenocoumarol in a sample of Lebanese people. Journal of Clinical Pharmacology, 51(10), 1418-28. https://doi.org/10.1177/0091270010382910
Esmerian MO, et al. Influence of CYP2C9 and VKORC1 Polymorphisms On Warfarin and Acenocoumarol in a Sample of Lebanese People. J Clin Pharmacol. 2011;51(10):1418-28. PubMed PMID: 21148049.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Influence of CYP2C9 and VKORC1 polymorphisms on warfarin and acenocoumarol in a sample of Lebanese people. AU - Esmerian,Maria O, AU - Mitri,Zahi, AU - Habbal,Mohammad-Zuheir, AU - Geryess,Eddy, AU - Zaatari,Ghazi, AU - Alam,Samir, AU - Skouri,Hadi N, AU - Mahfouz,Rami A, AU - Taher,Ali, AU - Zgheib,Nathalie K, Y1 - 2010/12/08/ PY - 2010/12/15/entrez PY - 2010/12/15/pubmed PY - 2012/1/27/medline SP - 1418 EP - 28 JF - Journal of clinical pharmacology JO - J Clin Pharmacol VL - 51 IS - 10 N2 - 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. SN - 1552-4604 UR - https://www.unboundmedicine.com/medline/citation/21148049/Influence_of_CYP2C9_and_VKORC1_polymorphisms_on_warfarin_and_acenocoumarol_in_a_sample_of_Lebanese_people_ L2 - https://doi.org/10.1177/0091270010382910 DB - PRIME DP - Unbound Medicine ER -