PEAR1 Genetic Variants Increase The Susceptibility Of Aspirin Resistance In The Chinese Patients With Ischemic Stroke

Background:Patients continue to experience thromboembolic events despite aspirin therapy,called aspirin resistance(AR)or treatment failure.The importance of genetic variants in AR is being increasingly recognized.Platelet Endothelial Aggregation Receptor-1(PEAR1)is a recently reported platelet transmembrane protein which plays an important role in platelet aggregation in some races.However,a genome-wide association study(GWAS)of platelet in Chinese has not been reported.The aim of this study was to investigate whether PEAR1 genetic variations were associated with aspirin resistance in Chinese patients treated with aspirin.Material/Methods: 450 patients with ischemic cerebrovascular disease who were treated with aspirin(100mg,≥7d)were enrolled in the study.Platelet aggregation was measured by thromboela-stography(TEG)and the result was defined as percent inhibition of platelet aggregation(IPA).All patients were divided into AR group(n=110)and AS group(n=340)according to the TEG diagnostic criteria(AR is defined as IPA<50%,AS is defined as IPA≥50%).3 single nucleotide polymorphisms(SNPs)of PEAR1(rs12041331rs1256888 rs2768759)were determined by polymerase chain reaction-restricted fragment length polymorphism(PCR-RFLP)and sequence methods.Haploview software was used to construct haplotypes,and the analysis was conducted.Results: The prevalence of aspirin resistance was 24.44%.The genotype and allele frequencies of rs12041331 rs2768759 gene polymorphisms were significantly different between AR group and AS group(P<0.05).Allele G at rs12041331(p = 0.01),Allele C at rs2768759(p=0.02)were associated with AR.There was no significant difference in rs1256888(P > 0.05).Additionally,according to the haplotype analysis,LD between rs12041331 and rs1256888 was very high(r2=0.818)and the haplotype TG(OR=1.390,95%CI=1.008-2.010)increased the risk of AR.Conclusions:PEAR1 genetic variations were strongly associated with AR in Chinese patients with with ischemic stroke.These genetic variations may contribute to the variabilityin platelet function,leading to ischemic stroke.