Human P2RY12 (P2Y purinoceptor 12) ELISA Kit

Objective: Investigate the association between P2Y12 Purinoceptor (P2RY12) polymorphisms and adverse clinical events in coronary artery disease (CAD) patients treated with clopidogrel. Methods: We performed a comprehensive database search, with a particular focus on P2RY12 polymorphisms and their effects on clopidogrel-treated CAD patients, in the PubMed, EMBASE, Cochrane Library, clinicaltrials. gov, Web of Science, and Chinese databases from their inceptions to April 8, 2017. The primary endpoints were composite ischemic events (including cardiovascular and cerebrovascular ischemic events), the secondary endpoints were independent cardiovascular events (mortality, non-fatal myocardial infarction, stent thrombosis, unstable angina, and target vessel revascularization) and the safety endpoints were bleeding events. Results: Overall 10 studies and 10,810 clopidogrel-treated CAD patients were studied in the present work. Subjects of the common alleles of P2RY12 polymorphisms showed higher risk for composite ischemic events compared to non-carriers (n = 434 of 3268[13.3%] vs. n = 646 of 6133[10.5%]; RR: 1.39, 95%CI: 1.14-1.69; p = 0.001). These allele carriers also showed increased risk for stent thrombosis (RR: 2.67, 95%CI: 1.03-6.91; p = 0.04), myocardial infarction (RR: 1.60, 95%CI: 1.06-2.42; p = 0.03), and unstable angina (RR: 1.72, 95%CI: 1.37-2.16; p < 0.00001) (vs. non-carriers). There was no significant difference between two groups in terms of mortality risk, target vessel revascularization or bleeding (p = 0.29; p = 0.48, respectively). Conclusions: P2RY12 gene polymorphisms might associate with higher risk of composite ischemic events, stent thrombosis, non-fatal myocardial infarction, unstable angina. While we found no significant effect on mortality, target vessel revascularization or bleeding.

Methods: The studied group comprises 124 patients with acute myocardial infarction on dual antiplatelet therapy with acetylsalicylic acid (ASA) and thienopyridines. Antiplatelet therapy was monitored by plateletrich plasma light transmittance aggregometry (LTA) using the APACT 4004 analyzer (Helena Laboratories) and by whole blood impedance aggregometry (multiple electrode aggregometry [ MEA]) using the Multiplate analyzer (Dynabyte). Platelet aggregation was detected after stimulation with arachidonic acid for detection of aspirin resistance and with adenosine diphosphate (ADP) and prostaglandin E-1 for detection of thienopyridine resistance. To determine the frequencies of P2Y12 (i-744T > C; rs2046934), P2Y12 (34C > T; rs6785930), COX-1 (-842A > G; rs10306114), GPVI (13254T > C; rs1613662), and GPIbA (5T > C; rs2243093) polymorphisms, DNA of patients with AIM was tested by real-time-polymerase chain reaction and melting curve analysis using the LightCycler 480 analyzer (Roche Diagnostics). Results: The cut-off points used for patients with effective ASA therapy are 25% of aggregated platelets and 220 area under the curve (AUC)/min if LTA or MEA, respectively. The cut-off points used for effective thienopyridine therapy are 45% of aggregated platelets or 298 AUC/min, respectively. Both LTA and MEA found that aspirin and thienopyridine therapies failed in 14.51% and 25.8%, respectively. The data were statistically processed using the SPSS version 15 software (SPSS, Inc.). Associations between receptor mutation status and response to therapy were assessed with Fisher's exact test. The significance level was set at 0.05. Conclusion: The aim of our work was to use the two functional laboratory methods described earlier to assess both aspirin and thienopyridine resistance and to determine the contribution of genetic polymorphisms of platelet receptors to resistance to antiplatelet therapy in AIM. Fisher's exact test showed a significant statistical correlation between platelet function tests suitable for monitoring ASA resistance, that is, LTA and MEA, and mutation status of COX1_A1 (-A842G). Fisher's exact test showed no statistically significant correlations between platelet function tests suitable for monitoring ASA resistance, that is, LTA and MEA, and mutation status of GP1bA (-5T > C) and GP6 (T13254C). Fisher's exact test showed no statistically significant correlation between mutational statuses of the receptors P2RY12 (i-T744C), P2RY12 (C34T), GP1bA (-5T > C), or GP6 (T13254C) and response to antiplatelet therapy with 75 mg of clopidogrel.