A037 Impact of the CYP2C19*17 allele on platelet response to clopidogrel in patients suffering from non–st elevation acute coronary syndrome - 17/04/09
Résumé |
Objectives |
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).
Background |
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.
Results |
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.
Conclusion |
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.
Le texte complet de cet article est disponible en PDF.Vol 102 - N° S1
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