Relationship Between CYP2C19*17Genotype Distribution And Platelet Aggregation, Bleeding Events In Clopidogrel-Treated Patients With Coronary Artery Disease

Objective: To assess the impact of CYP2C19*17allelic variant on plateletaggregation and bleeding events in clopidogrel-treated Chinese patients undergoingpercutaneous coronary intervention (PCI).Methods520patients undergoing PCI after pretreatment with300-mg clopidogreland aspirin were studied form January2010to April2011in Fujian ProvincialInstitute of Cardiovascular Disease.CYP2C19*17genotypes were determined withPCR-RFLP.5μmol/l adenosine diphosphate（ADP）induced platelet aggregation wasanalysed with platelet-rich plasma (PRP) and platelet-poor plasma (PPP) byturbidimetry method before and after10days treatment of clopidogrel. Results wererecorded as light transmission at maximal aggregation (Aggmax) and5min aggregation(Agglate) after the addition of ADP at final concentrations of5μmol/L. According tothe Thrombolysis in Myocardial Infarction (TIMI) criteria, the primary clinical safetyend point of the study was defined as the incidence of combined major and minorbleeding events throughout the follow-up period. All cases were followed up for7months (in median). The relationships between CYP2C19*17genetype and plateletaggregation along with bleeding events in clopidogrel-treated patients were analyzed.Results: For Chinese population, our study results were showed as followed:（1）About5.96%(31/520) of patients with bleeding events were observed, and thefrequency of CYP2C19*17allele was7.98%. The rate of bleeding in patients carrying CYP2C19*17allele (wt/*17and/*17/*17,n=71+6=77) was higher than those withwild-type genotype [wt/wt,14.29%(11/77) vs4.51%(20/443)，χ2test,p=0.0008];(2)First, At baseline, the5-μmol/L ADP-induced Aggmax, Agglateand Disaggregationhad no significant difference in three different CYP2C19*17genotypes,but10daysafter administration, the*17/*17(n=6) and wt/*17carriers(n=71) were foundsignificantly lower ADP-induced platelet aggregation values compared with wild-typehomozygotes (P<0.05and P<0.01,respective). Second, the IPA (Inhibition of plateletaggregation,IPA) in extensive metabolizer(EM,combine*17/*17with wt/*17）carrierswas higher than homozygotes (wt/wt, n=443,P<0.05and P<0.01respective); Thesame result was found in disaggregation of platelet10d after treatment.(3) Patientswith*17allele of CYP2C19had a higher ratio of bleeding than those with wild-typegenotype (wt/*17and*17/*17versus wt/wt: OR,1.95;95%CI,1.31to3.16,P=0.006), The risk of bleeding was highest in patients of CYP2C19*17homozygous,though only1(16.67%,1/6) bleeding event occurred.Conclusions: CYP2C19*17allele carrier is significantly associated with enhancedresponse to clopidogrel and an increased risk of bleeding.