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Studies On The Correlation Between Paraoxonase-1Gene Gln/Arg192Polymorphism And Clopidogrel Resistance

Posted on:2015-04-28Degree:MasterType:Thesis
Country:ChinaCandidate:G H CaoFull Text:PDF
GTID:2284330431975165Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Objective To investigate the correlation between PON-1(Paraoxonase-1) gene Gln/Arg192polymorphism to the occurrence of clopidogrel resistance (CR) in the patients of coronary atherosclerotic heart disease (CAHD) who underwent percutaneous coronary intervention (PCI) in Chinese Han population of Tianjin district.Methods:A case-control method was employed in our study. A total of260patients with chronic stable angina receiving dual antiplatelet treatment were enrolled in TianJin chest hospital for PCI from Noverber2010to May2013.The average age was (62.19±9.617) years, males170, female90, age range from33years to86years. The maximum rate of platelet aggregation (MPA) induced by ADP was detected by optical turbidimetric method, respectively in taking clopidogrel before, taking300mg loading dose of clopidogrel after24hours. The MPA after taking300mg loading dose of clopidogre less10%than baseline values was defined as clopidogrel resistance (CR).Accordingly, patients were then divided into CR group (n=54) and non-CR group(n=206).Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was carried out to determine PON-1gene Gln/Argl92polymorphism. According to PON-1gene Gln/Argl92polymorphism,260patients were divided into three groups:homozygous wild-type (R/R); mutant heterozygote (R/Q); homozygote (Q/Q).Then SPSS18statistical software was used for statistics and analysis the relationship of PON-1Gln/Arg192gene polymorphisms to clopidogrel resistance.Result:1. The MPA distribution before taking the medicine between20.33%68.64%, the average (38.85+7.928)%; taking300mg loading dose after24hours, the MPA distribution between2.43%-48.35%,the average (19.598+9.762)%;the reduce of MPA distribution between1.51%-62.8%, the average (19.31+9.81)%. In this study,the rate of clopidogrel resistance was20.8%. According to the reduce of MPA, patients were divided into CR group (n=54) and non-CR group(n=206). No significant different of basic clinical data was fond between two groups(P>0.05).2. In all the260patients, The frequencie of three genotype RR, QR and QQ was32.3%(84),55.8%(145),11.9%(31).The allele frequency of R was60.2%and the frequency of allele Q is39.8%. The differences between the predicted value and the actual observed value had no statistical significance (P>0.05) by examinating upon three genotypes distribution. The genotypes distribution in our study were in agreement with Hardy-Weinberg equilibrium suggests that samples was from a larger group, in a random mating equilibrium, a representative sample.3. According to PON-1gene Gln/Argl92polymorphism,260patients were divided into three groups:homozygous wild-type (R/R),84(32.3%); mutant heterozygote (R/Q),145(55.8%); homozygote (Q/Q),31(11.9%); No significant different of basic clinical data was fond among three groups(P>0.05).4.No significant differences of MAP,respectively before taking clopidogrel (P>0.05)、after24hours of taking300mg lording dose clopidogrel (P=0.055)、the reduce rate(P=0.960), was found among three genotypes.5. Three frequencies of genotype RR, QR and QQ were38.9%,50.0%,11.1%in CR group, and30.6%,57.3%,12.1%in NCR groups, respectively. No significant difference was found among three genotypes in CR groups (P<0.05).Conclusions:1. Platelet aggregation rate decreased in this study population after taking clopidogrel. The incidence of clopidogrel resistance was20.8%2. No significant differences of MAP,respectively before taking clopidogrel、 after24hours of taking300mg lording dose clopidogrel、the reduce rate was fond among three genotypes.3. No significant difference was found among three genotypes in CR groups (P<0.05).4. PON-1gene Gln/Argl92polymorphism has no correlation with clopidogrel resistance...
Keywords/Search Tags:clopidogrel resistance, paraoxonase-1, Gln/Arg192, genepolymorphism, platelet aggregation
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