The Relationship Between Clinical Events And The Gene Polymorphisms Of CYP2C19 And CYP2D6 In Patients After Percutaneous Coronary Intervention

Objective: To investigate the CYP2D6 gene polymorphism is influential to clopidogrel metabolism;Discussion about the correlation of CYP2C19 and CYP2D6 gene polymorphism with platelet reactivity and clinical events for patients who treated with clopidogrel after PCI.To make sure that whether patients could be predicted the reactivity to clopidogrel by detecting genotype early. In order to guiding reasonable and individualized antiplatelet therapy for patients.Methods: From January 2015 to December 2015,the clinical data of 344 patients who were successfully conducted the PCI surgery in Fujian Provincial Hospital were retrospectively analyzed. All patients were extracted DNA through tubular method. CYP2C19 and CYP2D6 genes were detected by DNA microarray chips. Blood samples were collected within 24 hours after PCI, if the patients were treated with tirofiban during operation, blood samples should be collected after 48 hours of stopping drugs. ADP inhibition rate was detected by TEG. Then follow-up of PCI postoperative patients of major adverse cardiac events(MACE) and bleeding events happening within 4months to 1 year.Due to the exclusion of interactions between drugs and gene inspection no results and lost to follow-up, 286 cases conformed to the requirement in the end. According to ADP inhibition rate,we divided the patients into two groups(ADP inhibition rate ≧70% for effect antiplatelet aggregation; the ADP inhibition rate﹤70% for low antiplatelet response),and compared the clinical data and two kinds of gene polymorphism of difference between the two group.Comparing of the correlation of CYP2C19, CYP2D6 genotype between the incidence of MACE and bleeding events, respectively.In order to further clear whether CYP2D6 gene affected the metabolism of clopidogrel or not, we proceeded with subgroup analysis. the CYP2C19 genotype were divided into two groups(wild type vs mutant type) to confirm whether the CYP2D6 gene variants increased bleeding events of CYP2C19 wild type group andb reduced the incidence of MACE CYP2C19 mutation group.Results:(1)The group In ADP inhibition rate≧70%, For CYP2D6 gene, the EM group, IM and PM group proportion gradually reduced, 52(48.6%) vs 56(40.3%) vs 9(22.5%), difference was statistically significant(P=0.016), the difference mainly comes from the EM and PM group(P=0.004);CYP2D6 different genotypes was no significant difference between the two groups for different ADP inhibition rate(P = 0.274).(2)For CYP2D6 gene,the EM group, the IM group and the PM group gradually increased incidence of bleeding events: 5(8.8%), 16(11.0%), 14(16.9%), but there was no statistically significant difference(P = 0.284).(3)In the normal wild type 107 patients of CYP2C19, CYP2D6 gene IM group, the PM group ADP inhibition rate were high in the EM group: 69.88±27.46,65.94± 22.35 vs 62.05±26.30 mm, but there was no statistically significant difference(P = 0.397).For CYP2D6 gene group, the EM group,the IM group, the PM group gradually increased incidence of bleeding events: 2(9.5%) vs 6(11.5%) vs 7(20.6%), but the difference was also not significant(P = 0.400).(4)In CYP2C19 gene mutation type 179 cases of patients, comparing different metabolic type CYP2D6 and ADP inhibition rate, the relationship between the incidence of MACE, there was no statistically significant difference(P = 0.362, the former to the latter(P = 0.447).(5)For CYP2C19 gene,the incidence of MACE for the IM group,and PM group were relatively higher than EM group: 26(18.7%), 7(17.5%) vs 7(6.5%), the difference was statistically significant(P= = 0.019), the difference mainly from EM and the IM group(P = 0.006).Multiariable Logistic regression analysis was carried out on the factors affecting MACE, find the CYP2C19*2/*3 carriers of PCI postoperative risk of the occurrence of MACE is 3.5 times that of the normal wild type(OR = 3.468, 95% CI: 1.465 8.206, P = 0.005).Conclusion: CYP2D6 *10 gene mutations had no obvious effect on clopidogrel metabolism,and they are not associated with antiplatelet efficacy of clopidogrel or clinical outcome.CYP2C19 * 2 or * 3 gene mutations impair the efficacy of clopidogrel antiplatele,and cause high platelet reactivity after PCI, and CYP2C19 * 2 or * 3 allele loss of function carriers have increased incidence of adverse cardiovascular events.