P2Y12 polymorphisms and antiplatelet effects of aspirin in patients with coronary artery disease

AIMS Recently, two genetic polymorphisms of the platelet ADP receptor P2Y(12) (haplotypes H2 and 34T) have been implicated in increased platelet aggregation and atherothrombotic risk. It was suggested that these polymorphisms contribute to a diminished response to antiplatelet drugs. Therefore, we investigated the effects of these polymorphisms on platelet aggregation in aspirin-treated patients with coronary artery disease (CAD). METHODS Platelet aggregation was studied in platelet-rich plasma from 124 patients with CAD treated with 100 mg aspirin day(-1). P2Y(12) ADP receptor polymorphisms were determined by PCR-RFLP. The 52G > T polymorphism was used as tag-SNP for the H2 haplotype. Aggregation was induced by 1 mg l(-1) collagen. In a subgroup (n = 72), a concentration-response curve to collagen (0.5-10 mg l(-1)), aggregation at 2 mu mol l(-1) ADP and 1 mmol l(-1) arachidonic acid were determined. RESULTS Whereas arachidonic acid-induced aggregation was inhibited in all patients, collagen and ADP-induced aggregation were highly variable. However, aggregation did not differ significantly between carriers and noncarriers of the 52T-allele (1 mg l(-1) collagen: 32.7% (21.9-38.6%) vs. 32.5% (21.2-41.6%); P = 0.77; ADP: 33.1% (29.9-40.9%) vs. 39.1% (31.5-49.7%); P = 0.34), respectively. EC50 values were 1.26 mg l(-1) (0.79-2.02) and 1.54 mg l(-1) (0.98-2.4) collagen in noncarriers and carriers of the H2 haplotype, respectively (P = 0.56). Moreover, the 34 degrees C > T polymorphism did not significantly affect any of the aggregatory responses. CONCLUSIONS Low-dose aspirin inhibits platelet aggregation to the same extent in patients carrying or not carrying the P2Y(12) H2 haplotype and/or the 34T allele. Our data do not support the hypothesis that these polymorphisms contribute to an attenuated antiplatelet effect of aspirin.