The Correlation Of Clopidogrel Resistance And PON1Q192R Gene Polymorphism In Han Population In Southern Hunan

Objectives:Study of the correlation of clopidogrel resistance and PON1Q192R genepolymorphism in han population in southern Hunan who suffer coronary arteryinterventional treatment of coronary heart disease patients, provide theoretical basisfor clinical individualized antiplatelet drug applications.Methods:A total of115patients undergoing PCI were enrolled in this study. Thosepatients involved were given loading dose of clopidogrel (300mg) and aspirin (300mg) before coronary angiography, and giving clopidogrel75mg/day, oral aspirin100mg/day at PCI postoperative. According to clopidogrel response which was assessedby post-treatment20μmol/L ADP-induced residual platelet agglutination (RPA),RPA≥70%was defined as clopidogrel resistance (CR). All the patients were takenperipheral blood leukocyte extract genomic DNA, using PCR-RFLP method, analysisof distribution of all the genotype and allele. All the patients had been given afollow-up visit for the second cardiovascular events (acute coronary syndrome attackand sudden cardiac death or hospitalization and incidence). Using the statisticalsoftware SPSS20discuss the correlation of clopidogrel resistance and Q192R PON1gene polymorphism.Results:1. All the patients ware separated into two groups,28patients of CR group and87patients of NCR group. No significant different of basic clinical data was fond among the two groups (p>0.05), While the activity of PON were significantly different(p<0.001).2. All genotypes distribution between the two groups were accord with Hardy-Weinberg genetic laws of balance. Three genotypes (QQ, QR, RR) distributionfrequency in CR group were42.86%(12cases),35.72%(10cases),21.43%(6cases),in the NCR group were17.24%(15cases),48.28%(42cases),34.48%(30cases), thedistribution of three kinds genotypes have significant differences between the twogroup (p<0.05); R allele and Q allele frequency between CR and NCR groupdistribution respectively60.71%,39.29%and41.38%,58.62%, and the distributionfrequency between the two groups have significant difference (p<0.05).3. Evaluated by logistic regression analysis, the Q192R genotype polymorphismsware the risk of CR.4. In the RR, QR, QQ three genetic mode, QQ genotype may be a risk factor ofclopidogrel resistance(OR=3.60，95%CI：1.45-8.91，p=0.005).5. Take the oxygen phosphorus as the substrate, determine PON enzyme activity ofpatients. In two groups, RR type PON enzyme activity were significantly higher inpatients with QQ type (p<0.001); With the same genotype, NCR group of PONenzyme activity was also significantly higher than that of CR group (p<0.001).6.115PCI patients had been given a follow-up visit and the second cardiovascularevents frequency is27.83%(32/115). There was statistical significance in patientswith the second cardiovascular events in two groups (p<0.001), between differentgenotypes of the second cardiovascular events frequency have significant differences(p<0.05).Conclusions:1. There was a relationship of PON1Q192R gene polymorphism and clopidogrelresistance, carrying Q allele may be a risk factor for clopidogrel resistance. 2. The activity of PON and clopidogrel resistance has certain relevance, the activityof PON was lower in patients with coronary heart disease are more likelyto occur with clopidogrel resistance.3. There was a relationship of clopidogrel resistance and the second cardiovascularevents, clopidogrel resistance in patients with the occurrence rate of adverse thesecond cardiovascular events in high. PON1Q192R gene polymorphism and thesecond cardiovascular events may have relevance.