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Archives of cardiovascular diseases
Volume 102, n° S1
page 20 (mars 2009)
Doi : 10.1016/S1875-2136(09)72170-9
Themes et posters

A037 Impact of the CYP2C19*17 allele on platelet response to clopidogrel in patients suffering from non–st elevation acute coronary syndrome

C. Frere 1, T. Cuisset 2, 1, P.-E. Morange 1, L. Camoin-Jau 3, J.-L. Bonnet 3, M.-C. Alessi 1, J.-S. Hulot 2
1 Inserm, U626, Faculté de Médecine, Marseille, France 
2 Department of Cardiology, CHU Timone, Marseille, France 
3 Laboratoire d’Hématologie, Hôpital de la Conception Marseille, France 


The aim of the study was to evaluate the impact of CYP2C19*17 on Platelet Response to Clopidogrel in patients suffering from Non-ST Elevation Acute Coronary Syndrome (NSTE ACS).


Clopidogrel is activated by cytochrome P450 (CYP) to generate an active metabolite that inhibits platelets through irreversible binding to the platelet P2Y12 receptor. We have shown that CYP2C19*2 is associated with a low platelet response to clopidogrel (Am J Cardiol 2008) , which has been demonstrated to predict adverse events in patients suffering from NSTE ACS. Recently, a novel allelic variant (CYP2C19*17) encoding an ultrarapid enzyme activity has been described.


We evaluated in 449 patients with non-ST elevation ACS after the administration of a loading dose of 600mg clopidogrel, the impact of CYP2C19*17 on platelet response to clopidogrel assessed by vasodilator stimulated phosphoprotein phosphorylation index (PRI VASP). No significant deviations from Hardy-Weinberg equilibrium were observed for this genetic variant. The observed frequency of the CYP2C19*17 allele was 20 %. The CYP2C19*17 allele was significantly associated with VASP, both in recessive (p =0.02) and codominant (p =0.0073) models. The CYP2C19*17 allele carriers (extensive metabolizers) exhibited the lowest PRI VASP (mean ± SD = 49.7±23.7 vs 55.9±22.8), testifying a better platelet response to clopidogrel. The interaction between the CYP2C19*2 (decrease in platelet response to clopidogrel) an the CYP2C19*17 allele (increase in platelet response to clopidogrel) was not significant.


The present data suggest that the CYPC19*17 allele influences platelet response to clopidogrel in patients with NSTE ACS, independently from the CYPC19*2 allele.

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