Investigation Of Relationship Of CYP2C19Gene Polymorphisms To Clopidogrel Resistance

Objective To investigate the relationship of CYP2C19gene polymorphisms to clopidogrel resistance in the patients of coronary atherosclerotic heart disease (CAHD) who accept percutaneous coronary intervention (PCI) in Chinese Han population of Tianjin district.Methods A total of120patients of CAHD who accept PCI from September2011to April2012in Tianjin Chest Hospital. There were80males case and40female cases while those mean age was (61.88±8.15) years, between from40years to79years. Detect the Max Platelet aggregation rate for2times while before take clopidogrel and after24hours of take300mg loading dose clopidogrel. Use the PCR-RFLP technology to genotype the CYP2C19gene polymorphisms in all the patients. According to the CYP2C19gene polymorphisms. Clopidogrel resistance was defined as the reduction of MPA<10%after24hours of take300mg loading dose clopidogrel.120patients ware divided into three groups:Extensive metabolizers (CYP2C19*1/*1), Intermediate metabolizers (CYP2C19*1/*2or*1/*3), Poor metabolizers (CYP2C19*2/*2or*3/*3or*2/*3). Then SPSS18statistical software was used for statistics and analysis the relationship of CYP2C19gene polymorphisms to clopidogrel resistance.Result:1. The mean MAP was (40.92±10.33)%, in between22.64%and68.64%, before take clopidogrel. After24hours of take300mg lording dose clopidogrel, The mean MAP was (22.51±10.34)%%, in between1.51%and49.78%. The rate of clopidogrel resistance was20.8%. All the patients ware separated into two groups,25patients of CR group and95patients of NCR group. No significant different of basic clinical data was fond among the two groups(P>0.05).2. In all the120patients, There were59patients (49.2%) carrying CYP2C19*2G/G,46patients (38.3%) CYP2C19*2G/A and15patients (12.5%) CYP2C19*2A/A. The allele frequency of G was68.3%and A was31.7%. There were113patients (94.2%) carrying CYP2C19*3G/G,3patients (2.5%) CYP2C19*3G/A and4patients (3.3%) CYP2C19*3A/A. The allele frequency of G was95.4%and A was4.6%. The allele frequencies in our study were in agreement with Hardy-Weinberg equilibrium. There were56(46.7%) patients divided into Extensive metabolizers group,44(36.7%) patient into Intermediate metabolizers group. Poor metabolizers group contain the rest of20(16.7%) patients.3. Compared to CYP2C19*2gene noncarriers, CYP2C19*2gene carriers have a higher MPA (19.01±7.96%vs22.80±10.94%vs30.25±10.50%, P=0.005), and a lesser reduction(20.59±9.47%vs18.59±9.80%vs9.88±8.92%, P=0.003) after24hours of take300mg lording dose clopidogrel. The MPA has no significant charge regardless of whether patients carry CYP2C19*3gene. After24hours of take300mg lording dose clopidogrel, Intermediate metabolizers group and Poor metabolizers group both have higher MPA than Extensive metabolizers group (19.21±7.93%vs23.36±11.49%vs27.35±10.53%,P=0.044), while have lesser reduction of MPA (20.62±6.31%vs19.84±9.16%vs12.24±2.30%, P=0.019).4. CR was present in13.6%patients (8cases) of CYP2C19*1/*1,21.7%patients (10cases) of CYP2C19*1/*2,46.7%patients (7cases) of CYP2C19*2/*2. CYP2C19*1/*2and CYP2C19*2/*2genotype carriers came up with a higher incidence of CR than CYP2C19*1/*1genotype carriers (P<0.05). No significant different of percentage of CR was fond regardless of whether patients carry CYP2C19*3gene. There ware2patients (3.6%) have CR expression in Extensive metabolizers group,12patients (27.3%) in Intermediate metabolizers group,9patients (45.0%) in Poor metabolizers group. The difference of CR distribution among the three groups was significative (P<0.05)5. Evaluated by logistic regression analysis, the CYP2C19*2genotype Polymorphisms(OR=7.765,95%CI:1.790-33.678,P=0.006) ware the risk of CR., while the CYP2C19*3genotype Polymorphisms has no relationship to CR.Conclusions There was may be a relationship of CYP2C19gene polymorphisms to clopidogrel resistance in the patients of CAHD who accept PCI in Chinese Han population of Tianjin district. CYP2C19*2gene polymorphism was an independent risk factor for CR.