Genetic Polymorphism Research On CYP2C19 Of CAD Patients In The Han Nationality Population Of Northern China

Part1Genetic Polymorphism Analysis of CYP2C19 of CAD Patients in the Han nationality population of Northern ChinaBackground:Many study found the correlation between clopidogrel metabolizer and CYP2C19 gene polymorphism in CAD patients. CYP2C19 gene polymorphism is a predictor of CR in patients with CAD, and will significantly increase risks of acute, subacute or later ST events which once happened can bring "disasters" to patients carrying loss-of-function CYP2C19 allele after Percutaneous coronary intervention (PCI).Objective:To explore the genetic polymorphism distribution feature of cytochrome P450 2C19 (CYP2C19) of CAD patients in the Han nationality population of Northern China and its correlation between clopidogrel resistance.Methods:A total of 858 patients with CAD without kinship admitted to our hospital from September 2013 to September 2014 were included in this study. CYP2C19 genetic polymorphism is analyzed by using polymerase chain reaction-restriction fragment length polymorphis (PCR-RFLP). Their adenosine diphosphate(ADP) induced platelet aggregation test (PAgT) was measured by light transmittance aggregometry (LTA) after admission and having taken 300mg clopidogrel 24 hoursl later. Compared the discharge PAgT of loading dose with admission, if the absolute value is equal to or less than 10% for CR, all patients are divided the into clopidogrel resistance (CR) and non-clopidogrel resistance (NCR) groups.Results:1、The frequency of mutation*2 and*3 are 30.5%、4.8%, respectively. The genotypes distribution of the groups are in the Hardy-Weinberg equilibrium(P>0.05). The incidence of homozygous wildtype extensive metabolizer is 41.8%, and that carriers with loss-of-function gene is 58.2%.The incidence of intermediate metabolizer (one mutant gene)、 poor metabolizer(two mutant genes) are45.7%、12.5%, respectively, and homozygous mutant poor metabolizer is 10.5%. No statistical significance is between different genotypes and genders.2、A total of 858 patients with CAD admitted are included in this study. There are 235 (27.4%) patents in the CR group, and 139 (59.1%) males; 623 cases in the NCR group,422 (67.7%) males. Significant difference is between two groups genders and platelet aggregation rate in the clinical baseline characteristics (P<0.05), no statistical difference between orthers (P>0.05).3、There are 235 (27.4%) patents in the CR group,81(34.5%) carriers with genotype *1/*1、93(39.6%) carriers with genotype *1/*2、23(9.8%) carriers with genotype *1/*3、31(13.2%) carriers with genotype *2/*2、7(3.0%) carriers with genotype *2/*3.The difference between clopidogrel response and carriers with CYP2C19 genotypes is significant, and the analysis indicate that there are less carriers with genotype *1/*1 in CR group.4、There are 81 (34.5%) carriers with extensive metabolizers(EM)、116(49.4%) carriers with intermediate metabolizers(IM)、and 38(16.2%) carriers with poor metabolizers(PM) in CR group. The difference between clopidogrel response and carriers with CYP2C19 metabolizers is significant, and the analysis indicates that there are less carriers with EM, and more carriers with one or two loss-of-function allele (IM or PM) in CR group.Conclusion:There are no significant difference in the distribution of CYP2C19 polymorphism between northern China and other areas of China. In CR group there are more carriers with one or two loss-of-function genotypes.Part 2Correlation between Clopidogrel Low Response and CYP2C19 Gene Polymorphism in CAD Patients after PCIBackground:At present many studies have shown that some patients with coronary artery disease (CAD) after percutaneous coronary intervention(PCI) even have taken standard dose of dual antiplatelet drug regularly long-term, thrombotic events also occurred. Clopidogrel low response are found in these patients by platelet function tests in laboratory. Study found that the liver enzyme CYP2C19 gene polymorphisms—the internal genetic factor which participatate in the metabolism of clopidogrel is associated with clopidogrel low response (CLR). The mechanism of CLR is not clear yet and the diagnosis of CLR can be divided into laboratory and clinical diagnosis. Laboratory test of platelet function is lack of higher specificity, and clinical diagnosis lags behind thrombotic events happened to patients. The occurrence of CLR is not very low.We give more attention to the lasting impacts on prognosis in patients taking clopidogrel after PCI which become a debate hot spot of dual antiplatelet drug.Objective:To explore the correlation between CLR and CYP2C19 gene polymorphism in CAD patients after PCI.Methods:A total of 247 patients with CAD after PCI admitted to our hospital from October 2013 to October 2014 were included in this study, and treated with dual antiplatelet drugs, aspirin and clopidogrel. The clopidogrel response is judged by depending on the AA and ADP-induced platelet inhibition rate tested by thromboelastogram (TEG). CLR is defined as the ADP-induced platelet inhibition rate less than 30% and equal to or more than 30% as clopidogrel sensitive. AA-induced platelet inhibition rate is less than 50% as aspirin resistance(AR) and equal to or more than 30% as non-aspirin resistance (NAR). The gene chip detection technology is used to detect the genotye of CYP2C19 to further explore the correlation between CLR and CYP2C19 gene polymorphism in CAD patients after PCI.Results:1、In these 247 patients, the ADP-induced platelet inhibition rate is significantly statistical difference between carriers with CYP2C19*1/*1 and CYP2C19*2/*2. extensive and poor metabolizers.2、The total occurrence of CLR is 36.8%(91 patients). There is significant difference between CLR and CYP2C19 genotyes、metabolizers. indicating that less patients with extensive metabolizer (CYP2C19*1/*1) in the clopidogrel sensitive group, more patients with intermediate or poor metabolizers in the CLR group.3、55 cases (22.2%) are both AR and CLR group; 36 cases (25.4%) in aspirin sensitive group are CLR. There is correlation between AP and CLR.Conclusion:There is correlation between CLR and CYP2C19 gene polymorphism、AR in CAD patients after PCI, more carriers with intermediate or poor metabolizers in the CLR group.