Impact Of CYP2C19 Gene Polymorphism On Platelet Function、imflammatory、endothelial Biomarkers And Prognosis In Patients Received Clopidogrel Therapy Undergoing Percutaneous Coronary Intervention

Objective To observe the residual platelet aggregation rate,maximum platelet aggregation rate, MMP-9, s VCAM-1, s E-selectin levels of patinents with different CYP2C19 gene who received clopidogrel dual antiplatelet therapy after percutaneous coronary intervention(PCI). To observe the effect of platelet, inflammation, endothelial biomarkers and CYP2C19 gene variation on the prognosis of patients after PCI.Metheods A total of 519 patients undergoing elective(PCI) were included. CYP2C19 gene type were tested before operation and the patients were divided into extensive metabolizers(EM), intermediate metabolizers(IM), poor metabolizers(PM) according to genotype. Loading dose of 300 mg clopidogrel, atorvastatin 40 mg were given at night before PCI. Blood samples were collected for detection after 24 h when the PCI was finished, Platelet aggregation rate was tested by the light transmittance aggregometry, patients’ peripheral serum were used to test the level of MMP-9,s VCAM-1,soluble E selectin level by enzyme-linked immunosorbent assay(ELISA). After PCI the patients’ follow-up was carried out through telephone, outpatient service and readmission. The occurrence of major adverse cardiovascular events as the end of follow-up, major adverse cardiovascular events were defined for unstable angina readmission, non fatal myocardial infarction and cardiac death.Results 1. The difference of residual platelet aggregation rate in extensive metabolizers, intermediate metabolizers, poor metabolizers is significant(median: 8.58, 15.89, 23.39 P<0.01). Extensive metabolizers is lower than intermediate metabolizers and poor metabolizers(all P <0.01), while no significant difference between intermediate metabolizers and poor metabolizers. The difference of maximum platelet aggregation rate are significant among three groups(median 24.49,33.04,33.66 P<0.01), extensive metabolizers is lower than intermediate metabolizers and poor metabolizers(all P<0.01), while no significant difference between intermediate metabolizers and poor metabolizers. 2. The difference of MMP-9 levels is significant among three groups(median 178.11,361.34,348.38 P<0.01), extensive metabolizers is lower than intermediate metabolizers and poor metabolizers(all P <0.01), while no significant difference between intermediate metabolizers and poor metabolizers. 3. The difference of s VCAM-1 levels is significant among three groups(median 175.25,216.63,233.91 P<0.01), extensive metabolizers is lower than intermediate metabolizers and poor metabolizers(all P <0.01), while no significant difference between intermediate metabolizers and poor metabolizers. 4. The difference of s E-selectin levels is significant among three groups(median 5.98,7,7 P<0.01), extensive metabolizers is lower than intermediate metabolizers and poor metabolizers(all P <0.01), while no significant difference between intermediate metabolizers and poor metabolizers. 5. The patients were divided into two groups which whether the occurrence of major cardiovascular events, multivariate regression analysis showed that genotype CYP2C19 in intermediate metabolism and poor metabolism are a major risk factor for cardiovascular adverse events, the value of OR= 2.450, 95%CI:1.299-4.619, P=0.006.Conclusion The polymorphism of CYP2C19 gene to reflect the effect of clopidogrel treatment in patients after PCI, the effect of clopidogrel on the patient who carry the CYP2C19 gene mutation(intermediate metabolism and poor metabolism) about the platelet activity, anti-inflammatory, endothelial protective effect and the prevention of major adverse cardiovascular events were not as good as the extensive metabolism.