Cytochrome P450 2C19 Polymorphisms and Clopidogrel Management in Patients with Coronary Artery Disease in Gaza Strip-Palestine

Abstract

Background: Platelets play a central role in the pathophysiology of the acute coronary syndromes following percutaneous coronary intervention (PCI). Clopidogrel is an oral thienopyridine derivative capable of inhibiting platelet activation. Clopidogrel is a prodrug that is converted into an active drug by the hepatic cytochrome CYP2C19. The CYP2C19*2 and the CYP2C19*3 polymorphic alleles are considered to be important loss-of-function alleles resulting in diminished response to Clopidogrel. Objective: The aim of this study was to determine the allelic frequency of CYP2C19 wild type allele (CYP2C19*1) and its loss of function variants (alleles *2 and *3), and their role in recurrence of cardiovascular disease in PCI patients receiving Clopidogrel in Gaza strip. Methods: This study is cross sectional study with convenience sample. Whole blood samples were collected from 110 patients undergoing PCI under clopidogrel therapy. The frequency of CYP2C19 alleles was determined by the polymerase chain reaction with restriction fragment length polymorphism (PCR-RFLP). Results: The frequency of CYP2C19*1, *2 and *3 alleles was 82.3%, 15.5% and 2.3% respectively. Genotyping analysis showed that, 67.3% were homozygotes for CYP2C19*1, 27.3 % were *1/*2, 2.7% with *1/*3 genotype, 1.8% were *2/*3 and 0.9% were *2/*2. These frequencies were comparable to those of other Caucasian populations. According to this study the poor metabolizers (PM) phenotype frequency was 2.7 %, which is in the same range reported in Caucasians (2 to 5%) and lower than Oriental populations 13-23%. A strong significant relation was found between stent restenosis and carrying the variant allele CYP2C19*2 (P= 0.001). On the other hand, there was no significant relation between stent restenosis and carrying the variant allele CY2C19*3 (p = 0.324). Conclusion: The CYP2C19*2 and CYP2C19*3 alleles genotyping should be included in the workup of patient considered for Clopidogrel therapy to avoid in-stent restenosis after PCI procedure.