Association Between IRS-1Gene Polymorphisms And Clopidogrel Resistance In Patients With Coronary Artery Disease And Type2Diabetes Mellitus

ObjectiveDual antiplatelet therapy with aspirin and clopidogrel is a main method oftreatment for preventing the occurrence of stent thrombosis nowadays.However, some patients who received standard antithrombotic therapy stillhaving thromboembolic. The mechanism of this phenomenon is not fullydemonstrated, genetic factors have a significant impact on the differences ofinterindividuals response to antiplatelet therapy. Patients with type2diabeteshave a higher incidence of thromboembolic compared with non-diabetes. It isbecause inhibition of platelet activity by insulin is decreased in diabetic patientsand platelet activity is significantly increased, antiplatelet medications is loss ofefficiency. Insulin receptor substrate1is an important intermediate in theinsulin signal transduction, which occupies an important position in theinhibition of platelet activation by insulin. Therefore, the present study is toinvestigate correlation of IRS1gene polymorphisms and clopidogrel resistancein patients with coronary artery disease and type2diabetes mellitus.Methods434patients with CAD and type2diabetes receiving standard antiplatelettherapy were enrolled in the study. According to clopidogrel response whichwas assessed by post-treatment20μmol/L ADP-induced residual plateletagglutination(RPA), RPA≥70%was defined as clopidogrel resistance (CR).Patients were grouped into CR and NCR group according to RPA value.Genomic DNA was extracted from peripheral blood of patients, the genotypesand allele frequencies of rs956115, rs1896832, rs1801278, rs1078533, rs13431554and rs2251692were detected by PCR and direct sequencing.Statistical analysis was performed with the SPSS version19.0software andSNPStats.ResultsThe genotype frequencies of SNPs (rs956115, rs1896832, rs1801278,rs1078533, rs13431554, rs2251692) in IRS1gene conformed to theHardy-Weinberg equilibrium in two groups. The genotypes and allelesfrequencies of rs13431554was different in CR and NCR group. No significantdifference was observed in genotypes and allele frequencies in the other5SNPs between the two groups (P>0.05). IRS1gene rs13431554polymorphism is concerned with CR in patients with coronary artery diseaseand type2diabetes mellitus.ConclusionsIRS1gene rs13431554polymorphism is concerned with CR in patientswith coronary artery disease and type2diabetes mellitus.