Associations of CYP2C19 and F2R genetic polymorphisms with platelet reactivity in Chinese ischemic stroke patients receiving clopidogrel therapy.

OBJECTIVES: Genetic variation has been considered a major contributor to the high variability in the response to dual antiplatelet therapy in patients with acute ischemic stroke or transient ischemic attack. Recently, incidences of ischemic stroke are increasing rapidly in China. We aimed to evaluate the influence of potential determinants on the response of antiplatelet therapy and adverse events in Chinese ischemic stroke patients receiving clopidogrel-aspirin treatment. METHODS: Based on the clopidogrel drug response pathway and the coagulation and anticoagulation function, we systematically selected 34 genetic polymorphisms in 12 candidate genes. Three hundred and eight patients were divided into 2 groups according to their degree of inhibition of platelet aggregation. Multivariate analysis was then performed to assess the influence of demographic, clinical and genetic factors on platelet reactivity in Chinese ischemic stroke patients. RESULTS: We found that polymorphisms in CYP2C19 and F2R genes were still significantly associated with platelet reactivity in Chinese ischemic stroke patients (P = 0.037 and 0.015). The newly identified rs168753 in F2R gene may influence the efficacy to clopidogrel-aspirin therapy for ischemic stroke patients. We also found that ischemic stroke patients with low level of inhibition of platelet aggregation had higher risk of recurrent ischemic events (P = 0.001). CONCLUSIONS: Together, these results emphasized the necessity of genotype-directed antiplatelet therapy and facilitated to minimize adverse ischemic events.

Study of the Association of PEAR1, P2Y12, and UGT2A1 Polymorphisms with Platelet Reactivity in Response to Dual Antiplatelet Therapy in Chinese Patients.

OBJECTIVES: Genetic variation is thought to contribute to considerable interindividual variability in platelet function, and there is a pressing need to identify genetic markers that can be used to predict the response to treatment. Our study investigated whether PEAR1, P2Y12, and UGT2A1 polymorphisms were associated with platelet reactivity in response to dual antiplatelet therapy in Chinese patients with acute coronary syndrome. METHODS: Patients with inhibition of platelet aggregation (IPA) < 30% after treatment were classified as the high platelet reactivity (HPR) group. Patients with IPA > 30% were classified as the normal platelet reactivity (NPR) group. ADP-induced platelet aggregation was measured by thromboelastography (TEG) platelet-mapping assay. Thirteen single nucleotide polymorphisms (SNPs) of PEAR1, P2Y12 and UGT2A1 were genotyped using the Mass-ARRAY platform. RESULTS: Seven SNPs were significantly associated with ADP-induced platelet aggregation by univariate analysis. Major allele G at rs12041331, minor allele G at rs2644592, minor allele C at rs11264580, and minor allele C at rs11249454 were significantly associated with HPR, whereas minor allele T at rs57731889, minor allele A at rs16863356, and minor allele T at rs7634096 were significantly associated with NPR. The mean IPA was significantly lower in patients suffering recurrent ischemic events than in patients without recurrent events in our study (p = 0.048). CONCLUSIONS: Our findings suggest that PEAR1, P2Y12, and UGT2A1 genetic variants may be potential biomarkers that can be used to guide clinical applications of clopidogrel and aspirin in Chinese patients.