Abstract 2383: The Antiplatelet Effect Of Clopidogrel Is Associated With CYP2C19 *2 And *3 Polymorphism But Not With Pon-1 Q192R Polymorphism In Japanese Patients Undergoing neurointervention
Background Patients with cervical carotid or intracranial stenting are routinely premedicated with antithrombotic agents, clopidogrel and aspirin (ASA). A recent study has showed paraoxonase-1 (PON-1) Q192R genotypes impacts on antiplatlet effect of clopidogrel rather than CYP2C19 mutation. We investigate the influence of CYP2C19 *2, *3, and PON-1 Q192R genotypes on antiplatelet effect of clopidogrel in Japanese patients scheduled for neurointervention such as extracranial carotid artery stenting, intracranial artery stenting, or coil embolization of the cerebral aneurysm.
Method A total of 102 consecutive patients scheduled for neurointervention and treated with ASA and clopidogrel were enrolled. Genotyping of three single-nucleotide polymorphisms (SNPs) defining the two major CYP2C19 alleles *2, *3 and PON-1 Q192R was performed with the use of TaqMan® SNP Genotyping Assays (Applied Biosystems, CA) from stored DNA. Antiplatlet effect of clopidogrel was assessed by VerifyNow P2Y12 assay.
Result The frequencies of CYP2C19 *1/*1, *1/*2, *1/*3, *2/*2, *2/*3, and *3/*3 were 28 (27.5%), 39 (38.2%), 13 (12.7%), 9 (8.8%), 11 (10.8%), and 2 (2.0%), respectively. On the basis of CYP2C19 genotype, 28 patients (27.5%) were classified as an extensive metabolizer (EM), 52 (51.0%) as an intermediate metabolizer (IM) and 22 (21.6%) as a poor metabolizer (PM). The proportion of patients harboring CYP2C19 loss of function SNPs is 72.5%. The frequencies of PON-1 QQ192, QR192, and RR192 were 8 (7.8%), 52 (51.0%), and 42 (41.2%), respectively. P2Y12 reaction unit (PRU) in the VerifyNow P2Y12 assay was significantly higher in patients with CYP2C19 loss of function SNPs than those without (253.6±100.2 vs. 161.3±85.5, P<0.001). However, the PRU in patients with QR192 or RR192 were not significantly different from those with QQ192 ( 227.0±128.1 vs. 228.8±103.0, P=0.973).
Conclusion: In Japanese patients undergoing neurointervention, antiplatlet effect of clopidogrel was associated with CYP2C19 genotype *2and *3 but not with PON-1 Q192R genotype.
- © 2012 by American Heart Association, Inc.