Molecular Biology Reports

, Volume 38, Issue 8, pp 5449–5452

Prevalence of CYP2C19 polymorphisms in the Lebanese population

  • Isabelle Djaffar Jureidini
  • Nabil Chamseddine
  • Sose Keleshian
  • Rania Naoufal
  • Laila Zahed
  • Noha Hakime


Clopidogrel is one of the most commonly prescribed drugs, as its combination with low-dose aspirin is the recommended oral anti-platelet therapy, to prevent ischaemic events following coronary syndromes or stent placement. Numerous recent studies have shown that polymorphisms in the gene encoding the cytochrome P450 (CYP450) 2C19 enzyme (CYP2C19) contribute to variability in response to clopidogrel; patients with certain common genetic variants of CYP2C19 (*2, *3) have a reduced metabolism of clopidogrel and have a higher rate of cardiovascular events or stent thrombosis compared to patients with the CYP2C19 (*1) allele. CYP2C19*2 is most common in Caucasians, Africans and Asians while CYP2C19*3 has been found mostly in Asians. Since the prevalence of these variants in the Lebanese population has not yet been reported, our aim was to determine the genotypes of CYP2C19 in our population. CYP2C19 (*1/*2/*3) variants were assessed by Polymerase Chain Reaction-Restriction Length Polymorphism (PCR–RFLP) assays in a representative sample of 161 unrelated healthy Lebanese volunteers. The allele frequencies of CYP2C19 *2 and *3 were 0.13 and 0.03. Carriers of the CYP2C19 *2 or *3 represented 24.2% of the subjects. Our data show no significant difference in the frequency of CYP2C19 allelic variants when compared to Caucasian populations and demonstrate that the application of the recent FDA recommendations would also be beneficial in Lebanon, allowing physicians to identify patients at high risk for atherothrombotic events, and eventually advising them to consider other antiplatelet medications or alternative dosing strategies in poor metabolizers.


CYP2C19 Polymorphisms Lebanese PCR–RFLP 


  1. 1.
    Patrono C, Bachmann F, Guetta V et al (2004) Expert consensus document on the use of antiplatelet agents. Eur Heat J 25:166–181CrossRefGoogle Scholar
  2. 2.
    Plavix (clopidogrel bisulfate) 75 mg tablets (2009) Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER). Available at Accessed June 19 2009
  3. 3.
    Antman EM, Hand M, Armstrong PW et al (2008) Focused update of the ACC/AHA 2004 guidelines for the management of patients with ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 51:210–247PubMedCrossRefGoogle Scholar
  4. 4.
    Anderson JL, Adams CD, Antman EM et al (2007) ACC/AHA 2007 guidelines for the management of patients with unstable angina/non ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non ST-Elevation Myocardial Infarction): developed in collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons: endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine. Circulation 116(7):e148–e304PubMedCrossRefGoogle Scholar
  5. 5.
    Chen ZM, Jiang LX, Chen YP et al (2005) Addition of clopidogrel to aspirin in 45, 852 patients with acute myocardial infarction: randomised placebo-controlled trial. Lancet 366:1607–1621PubMedCrossRefGoogle Scholar
  6. 6.
    Sabatine MS, Cannon CP, Gibson CM et al (2005) Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation. N Engl J Med 352:1179–1189PubMedCrossRefGoogle Scholar
  7. 7.
    Yusuf S, Zhao F, Mehta SR et al (2001) Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 345:494–502PubMedCrossRefGoogle Scholar
  8. 8.
    Steinhubl SR, Berger PB, Mann JT III et al (2002) Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized trial. JAMA 288:2411–2420PubMedCrossRefGoogle Scholar
  9. 9.
    Angiolillo DJ, Alfonso F (2007) Platelet function testing and cardiovascular outcomes: steps forward in identifying the best predictive measure. Thromb Haemost 98:707–709PubMedGoogle Scholar
  10. 10.
    Gurbel PA, Becker RC, Mann KG, Steinhubl SR, Michelson AD (2007) Platelet function monitoring in patients with coronary artery disease. J Am Coll Cardiol 50:1822–1834PubMedCrossRefGoogle Scholar
  11. 11.
    Wang TH, Bhatt DL, Topol EJ (2006) Aspirin and clopidogrel resistance: an emerging clinical entity. Eur Heart J 27:647–654PubMedCrossRefGoogle Scholar
  12. 12.
    Angiolillo DJ, Fernandez-Ortiz A, Bernardo E et al (2004) PIA polymorphism and platelet reactivity following clopidogrel loading dose in patients undergoing coronary stent implantation. Blood Coagul Fibrinolysis 15:89–93PubMedCrossRefGoogle Scholar
  13. 13.
    Angiolillo DJ, Fernandez-Ortiz A, Bernardo E et al (2006) Contribution of gene sequence variations of the hepatic cytochrome P450 3A4 enzyme to variability in individual responsiveness to clopidogrel. Arterioscler Thromb Vasc Biol 26:1895–1900PubMedCrossRefGoogle Scholar
  14. 14.
    Brandt JT, Close SL, Iturria SJ et al (2007) Common polymorphisms of CYP2C19 and CYP2C9 affect the pharmacokinetic and pharmacodynamic response to clopidogrel but not prasugrel. J Thromb Haemost 5:2429–2436PubMedCrossRefGoogle Scholar
  15. 15.
    Fontana P, Dupont A, Gandrille S et al (2003) Adenosine diphosphate-induced platelet aggregation is associated with P2Y12 gene sequence variations in healthy subjects. Circulation 108:989–995PubMedCrossRefGoogle Scholar
  16. 16.
    Giusti B, Gori AM, Marcucci R et al (2007) Cytochrome P450 2C19 loss-of-function polymorphism, but not CYP3A4 IVS10 + 12G/A and P2Y12 T744C polymorphisms, is associated with response variability to dual antiplatelet treatment in high-risk vascular patients. Pharmacogenet Genomics 17:1057–1064PubMedCrossRefGoogle Scholar
  17. 17.
    Hulot JS, Bura A, Villard E et al (2006) Cytochrome P450 2C19 loss-of-function polymorphism is a major determinant of clopidogrel responsiveness in healthy subjects. Blood 108:2244–2247PubMedCrossRefGoogle Scholar
  18. 18.
    Taubert D, von Beckerath N, Grimberg G et al (2006) Impact of P-glycoprotein on clopidogrel absorption. Clin Pharmacol Ther 80:486–501PubMedCrossRefGoogle Scholar
  19. 19.
    Trenk D, Hochholzer W, Fromm MF et al (2008) Cytochrome P450 2C19 681G > A polymorphism and high on-clopidogrel platelet reactivity associated with adverse 1-year clinical outcome of elective percutaneous coronary intervention with drugeluting or bare-metal stents. J Am Coll Cardiol 51:1925–1934PubMedCrossRefGoogle Scholar
  20. 20.
    Clarke TA, Waskell LA (2003) The metabolism of clopidogrel is catalyzed by human cytochrome P450 3A and is inhibited by atorvastatin. Drug Metab Dispos 31:53–59PubMedCrossRefGoogle Scholar
  21. 21.
    Robarge J, Fletcher R, Nguyen A, Thorn C (2006) Important Haplotype Information for CYP2C19. Pharmacogenomics Knowledge Base. Accessed 30 Sept 2006
  22. 22.
    Smith SM, Judge HM, Peters G et al (2006) Common sequence variations in the P2Y12 and CYP3A5 genes do not explain the variability in the inhibitory effects of clopidogrel therapy. Platelets 17:250–258PubMedCrossRefGoogle Scholar
  23. 23.
    Tabassome S, Verstuyft C, Mary-Krause M et al (2009) Genetic determinants of response to clopidogrel and cardiovascular events. N Engl J Med 360:1–13CrossRefGoogle Scholar
  24. 24.
    Mega J, Close S, Wiviott S et al (2009) Cytochrome p-450 polymorphisms and response to clopidogrel. N Engl J Med 360:354–362PubMedCrossRefGoogle Scholar
  25. 25.
    Fontana P, Senouf D, Mach F (2008) Biological effect of increased maintenance dose of clopidogrel in cardiovascular outpatients and influence of the cytochrome P450 2C19*2 allele on clopidogrel responsiveness. Thromb Res 121:463–468PubMedCrossRefGoogle Scholar
  26. 26.
    Sameer AEI, Amany GM, Abdela AA, Fadel SA (2009) CYP2C19 genotypes in a population of healthy volunteers and in children with hematological malignancies in gaza strip. Can J Clin Pharmacol 16(1):156–162Google Scholar
  27. 27.
    Zand N, Tajik N, Hoormand M, Moghaddam A, Milanian I (2005) Allele frequency of CYP2C19 gene polymorphisms in a healthy Iranian population. Int J Pharm Technol 4:124–128Google Scholar
  28. 28.
    FDA Drug Safety Communication: Reduced effectiveness of Plavix (clopidogrel) in patients who are poor metabolizers of the drug (2010) Safety Announcement Accessed 25 March 2010
  29. 29.
    Flockhart DA (2007) Drug interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine. Accessed 12 Jan 2009

Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Isabelle Djaffar Jureidini
    • 1
  • Nabil Chamseddine
    • 2
  • Sose Keleshian
    • 1
  • Rania Naoufal
    • 1
  • Laila Zahed
    • 1
  • Noha Hakime
    • 1
  1. 1.Department of Clinical LaboratorySaint George Hospital University Medical CenterBeirutLebanon
  2. 2.Onco-HematologySaint George Hospital University Medical CenterBeirutLebanon

Personalised recommendations