Prevalence and types of genetic polymorphisms of CYP2C19 and their effects on platelet aggregation inhibition by clopidogrel.

Objective: The current study was conducted to determine the distribution of genetic polymorphisms in CYP2C19 in Iraqi patients and their role in inter-individual variability of clopidogrel efficacy.

Patients And Methods: A prospective controlled study was done on 100 patients under high risk of cardiovascular diseases who started clopidogrel prophylactic therapy. Polymerase chain reaction-restriction fragment length polymorphism method was used to determine the existence of the CYP2C19 gene mutation. Vasodilator-stimulated phosphoprotein (VASP) index baseline besides one-month post-therapy was analyzed by dual-color flow cytometry analysis.

Results: Eight gene mutations of CYP2C19 were found (*1/*1), (*1/*2), (*1/*3), (*1/*8), (*1/*17), (*2/*2), (*2/*4), and (*3/*3) with higher prevalent CYP2C19*1 gene. Homozygous CYP2C19*1 allele was shown to be the rapid metabolizer comparing to the heterozygous CYP2C19*1 allele, whereas, CYP2C19*2 and CYP2C19*3 were resistant alleles and were present in 28% of patients. The analysis of VASP phosphorylation produces accurate inter-individual response variability in platelets inhibition by antiplatelet drugs.

Conclusions: In vitro gene analysis and VASP index improve the clinical outcome of a patient candidate to clopidogrel as prophylaxis in cardiovascular events.