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

Q.A.A. Aga, M.K. Hasan, K.F. Nassir, L.A.A. Aga, B.A. Al-Jaidi, M. Aldhoun, M.A. Morsy, A.B. Nair

Department of Pharmaceutical Sciences, Faculty of Pharmacy, Philadelphia University, Amman, Jordan. qutaiba975@gmail.com

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• Pharmacology

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.

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