ASSOCIATION OF THE G681A POLYMORPHISM OF CYP2C19 GENE WITH RESPONSE VARIABILITY TO DUAL ANTIPLATELET TREATMENT IN HIGH RISK VASCULAR DISEASE PATIENTS
Abstract number: O-W-011
Giusti1 B., Gori1 A.M., Marcucci1 R., Sestini1 I., Saracini1 C., Paniccia1 R., Valente1 S., Antoniucci2 D., Abbate1 R., Gensini1 G.F.
11Department of Medical and Surgical Critical Care, University of Florence 22Division of Cardiology, Careggi Hospital, Florence, Italy
How-to-cite Giusti B, Gori AM, Marcucci R, Sestini I, Saracini C, Paniccia R, Valente S, Antoniucci D, Abbate R, Gensini GF. ASSOCIATION OF THE G681A POLYMORPHISM OF CYP2C19 GENE WITH RESPONSE VARIABILITY TO DUAL ANTIPLATELET TREATMENT IN HIGH RISK VASCULAR DISEASE PATIENTS. J Thromb Haemost 2007; 5 Supplement 2: O-W-011
Abstract
Introduction: Response variability to antiplatelet treatment has been described and the widespread use of aspirin and clopidogrel requires clarification of the residual platelet reactivity (RPR) phenomenon. Polymorphisms of genes coding platelet components have been investigated, but the influence on platelet reactivity in high risk vascular patients on dual antiplatelet treatment is not still elucidated.
Aim of the study was to evaluate the effect of the following polymorphisms on modulating platelet function in acute coronary syndrome (ACS) patients on dual antiplatelet treatment: T744C (rs2046934) of P2Y12, IVS10+12G/A (rs2242480) of CYP3A4 and G681A (rs4244285) of CYP2C19 gene.
Methods: We measured platelet function by platelet-rich-plasma aggregation in 600 ACS patients. Microarray technology was used for the analysis of the three polymorphisms.
Results: G681A CYP2C19 polymorphism, but not the other investigated polymorphisms, was associated with higher platelet reactivity. Carriers of the rare allele (681A) of CYP2C19 polymorphism had significantly higher platelet aggregation values after 2mMADP (681GG 28%,range 16-45% vs 681GA+AA 38%,range 21-64%;p=0.001), 10mMADP (681GG 52%,range 35-65% vs 681GA+AA 60%,range 42-74%;p=0.002) and AA (681GG 11%,range 8-19% vs 681GA+AA 15%,range 9-74%;p=0.022) stimuli. The genotype distribution of CYP2C19 polymorphism significantly differed between patients with and without RPR evaluated by 10mMADP induced platelet aggregation (681GG 58.9%,681GA+AA 41.1% vs 681GG 71.5%,681GA+AA 28.5%;p=0.025) and by AA induced platelet aggregation (681GG 59.7%, 681GA+AA 40.3% vs 681GG 71.5%, 681GA+AA 28.5%;p=0.018). The genotype distribution of P2Y12 and CYP3A4 polymorphisms was similar in patients with and without RPR.
Conclusions: In conclusion, this study demonstrates for the first time, in high risk vascular patients, that the 681A allele of the CYP2C19 gene is associated with higher platelet aggregability and with residual platelet reactivity in patients on dual antiplatelet treatment.
