Correlation Evaluation And Structural Equation Model Construction Between Clopidogrel Gene Polymorphism And High On-treatment Platelet Reactivity In Patients After Percutaneous Coronary Intervention

The incidence of chronic non-communicable diseases,especially cardiovascular diseases,has increased with the development of social economy.Acute coronary syndrome(ACS)has become a serious public health problem.At present,percutaneous coronary intervention(PCI)is the main method for the treatment of ACS,while the major adverse cardiovascular events(MACE)related to thrombosis remains a thorny issue after PCI in the clinical setting.In China,clopidogrel is still the first-line antiplatelet agent after PCI due to economic factor.Whereas,the genetic polymorphisms of clopidogrel could affect its pharmacokinetics and pharmacodynamics across the whole process of absorption,metabolism and bioactivity.Genetic polymorphism has significant ethnic differences.The allele gene frequency of CYP2C19~*2 in Caucasians is 12-15%,while those in Asians is as high as 29%.Studies of Caucasians have shown that the risk of high on-treatment platelet reactivity(HTPR)and MACE in carriers with lost-function of CYP2C19 is higher than that in non-carriers.However,the results in Chinese population are not in line with that in Caucasians.Thus,it is important to clarify the relationship between clopidogrel gene polymorphism and HTPR in Chinese population after PCI.This study will be carried out as the following contents to clarify the relationship between clopidogrel gene polymorphism and HTPR in Chinese population after PCI,as well as to construct the structural equation model(SEM)of HTPR.Chapter 1: This section will review the gene polymorphism and HTPR in East Asian population,in order to guide further research direction in this field.In addition,we will clarify the study significance and study contents.Chapter 2: To explore the risk factors of HTPR in patients after PCI and also to explore predicted ability of these independent risk factors for HTPR.The main purpose of this section is to clarify the impact of clinical factors,coronary artery disease factors and surgical instruments factors in HTPR,so as to provide research basis for the construction of SEM in the later stage.Chapter 3: On the gene level,we will discuss the effect of gene polymorphism of Paraoxonase-1(PON-1)on HTPR in patients after PCI.The main purpose of this section is to determine whether the PON1 gene polymorphism will results in HTPR,providing a basis for the factor screening in the later SEM construction.Chapter 4: On the gene level,we will also discuss the effect of gene polymorphism of Platelet Endothelial Aggregation Receptor-1(PEAR1)on HTPR in patients after PCI.The main purpose of this section is to determine whether the PEAR1 gene polymorphism will results in HTPR,providing a basis for the factor screening in the later SEM construction.Chapter 5: On the basis of gene factors,clinical factors,coronary artery disease factors and instruments factors,the multiple linear regression equation will be used to establish the linear prediction model of HTPR for patients after PCI.The main purpose of this section is to establish the HTPR linear prediction formula for providing the model basis on screening high risk population of HTPR in clinic.Chapter 6: On the basis of above results,we will build the HTPR structural equation model(SEM).The main purpose of this section is to build the HTPR SEM,providing the model basis on screening high risk population of HTPR in clinic.Chapter 7: We will summarize the research results and provide the suggestion for further studies in this field.