Study On Diversity Of Platelet Function And Genetic Polymorphism In Patients Treat With Clopidogrel

Clopidogrel,an effective platelet aggregation inhibitors which can reducecardiovascular events and subacute thrombosis formated in braces obviously,isgenerally used in coronary heart disease(CHD) and percutaneous coronary intervention(PCI).But some studies indicated5%-30%patients show hypoergia even anergy afterusing clopidogrel.These patients have higher incidence rate of terminus events,includingcardiovascular death and re-infarction.The mechanisms of the curative effect variabilityof clopidogrel are complicated and not completely understood.Potential causes mayinclude genetic polymorphisms.Objective:To investigate the correlativity among the genetic polymorphisms(/coexisting polymorphisms) of CYP3A5*322893G>A，CYP2C19*2681G>A andP2Y12*1744T>C, functional detection of platelet and clopidogrel curative effectvarisbility in patients with coronary disease after PCI.Methods:1.118CHD patients who accepted PCI and detected the platelet functionby PlateletMappingTMafter PCI were adopted in Chinse PLA General Hospital fromNovember2010to March2011.The patients were divided into ischemia event relapsegroup(IERG) and non-ischemia event relapse group(NIERG) according to whether ornot the relapse of ischemia events in6monthes after PCI.Comparing the plateletinhibition ratio between the two groups to comprehend the evaluation function ofPlateletMappingTMfor clopidogrel curative effect varisbility.2.DNA was extractedfrom the samples which had been used for PlateletMappingTM,used to analyze thecorrelativity between the three genes above and the clopidogrel curative effectvariability by polymerase chain reaction and gene sequencing.3. According to theretrospective investigation into clinical reeords of the research objects, the clinicalcharacteristics of different clinical patterns in patients with CHD were analyzed.Results：1.Compared with UAP group and SAP group,the value of WBC,CK,CK- MB,DD,CRP and the proportion of smoker wre higher in AMI group significantly.2.26.27%of the patients occurred ischemia events during follow-up period.Thedifference of clinical characteristics between IERG and NIERG had no statisticallysignificant.3. PlateletMapping results showed， compared with NIERG the ADP-induced platelet inhibition ratio(PIR) in IERG was obviously lower(31.33%±24.91%vs54.68%±26.63%,P<0.05).It was found that the PIR of patients carrying mutant allele ofCYP3A5*3(41.98%±29.33%vs52.89%±26.49%)，2C19*2(43.15%±27.97%vs55.89%±26.71%) and P2Y12*1(38.74%±24.36%vs52.19%±28.58%) were lower thanpatients with wildtype.4. The frequency of ischemia event relapse in patients with Amutant allele of CYP3A5*3and2C19*2were43.64%and40.79%, which wassignification higher than patients carrying G/G genotype with frequency of20.99%and19.38%,but there was no signification difference between T/T genotype and C allele ofP2Y12*1(26.63%vs24.32%,P>0.05).5.Compared with control group(both G/G geno-type),the coexistence of the A allele of the G22893A polymorphism of CYP3A5and theA allele of the G22893A polymorphism of CYP2C19was associated with higher rate ofischemia events(55.56%vs5.13%,p<0.05).Conclution：1.Some indexs such as smoker,WBC,CK,CK-MB,DD,CRP canpredict the pathogenetic condition severity level and clinical type of the patients withCHD.2.The ADP-induced PIR detected by PlateletMappingTM,the rate of ischemiaevents and the genetic polymorphism of CYP3A5*3and CYP2C19*2had notablecorrelativity.PlateletMappingTMcan predict the ischemia event relapse on a certaindegree by detecting platelet function.3.The genetic polymorphisms especiallycoexisting polymorphisms of CYP3A5*3and2C19*2but not P2Y12*1play animportant role in clopidogrel curative effect varisbility.The detect of polymorphism maybecome an important method for risk evaluation of patients with CHD.