Drugs Aging 2007; 24 (4): 345-350 ORIGINAL RESEARCH ARTICLE 1170-229X/07/0004-0345/$44.95/0  2007 Adis Data Information BV. All rights reserved. Does Glycoprotein IIIa Gene (Pl A ) Polymorphism Influence Clopidogrel Resistance? A Study in Older Patients Elod Papp, 1 Viktoria Havasi, 2 Judit Bene, 2,3 Katalin Komlosi, 2 Gabor Talian, 2 Gergely Feher, 1 Beata Horvath, 1 Laszlo Szapary, 4 Kalman Toth 1 and Bela Melegh 2 1 First Department of Medicine, School of Medicine, University of Pecs, Pecs, Hungary 2 Department of Medical Genetics and Child Development, School of Medicine, University of Pecs, Pecs, Hungary 3 Hungarian Academy of Sciences Clinical Genetic Research Group, Pecs, Hungary 4 Department of Neurology, School of Medicine, University of Pecs, Pecs, Hungary Background: Clopidogrel is a potent antiplatelet drug used for secondary preven- Abstract tion after ischaemic cardiovascular or cerebrovascular events. In patients with aspirin (acetylsalicylic acid) intolerance or resistance, it is used as monotherapy. Recent data report that Pl A polymorphism of the glycoprotein IIIa gene may account for differences in aspirin-induced antiplatelet effects. An increased degree of platelet reactivity was also reported in Pl A2 carriers compared with Pl A1/A1 patients after administration of a clopidogrel 300mg loading dose. Objectives: The aim of this study was to assess the modulatory effect of the Pl A2 allele on platelet aggregation in patients taking long-term clopidogrel. Methods: The prevalence of the Pl A2 allele was assessed in 38 (21 males, 17 females; mean age 63 ± 13 years) clopidogrel-resistant and 59 (26 males, 33 females; mean age 63 ± 11 years) clopidogrel-responsive patients. The polymer- ase chain reaction-restriction fragment length polymorphism method was utilised to evaluate Pl A polymorphism. A Carat TX4  optical platelet aggregometer (Carat Diagnostics Ltd, Budapest, Hungary) was used to measure 5 and 10 μmol/L adenosine diphosphate-induced platelet aggregation. Results: Significantly more patients were taking combination antiplatelet therapy in the clopidogrel-resistant group than in the clopidogrel-responsive group (50% vs 30%, respectively). The prevalence of the Pl A2 allele did not differ significantly between the two groups (0.09 vs 0.13), even after adjustment for combination therapy and various risk factors. Conclusions: Our results show that carriers of the Pl A2 allele do not have an increased risk of clopidogrel resistance. These findings and data from our previ- ous studies suggest that patients with a Pl A2 allele homozygosity may benefit from antiplatelet therapy based on clopidogrel rather than aspirin.