Study On The Relationship Between PEAR1 Gene Polymorphism And Clopidogrel Resistance

Objective:To study the relationship between single nucleotide polymorphisms of Platelet Endothelial Aggregation Receptor-1(PEAR1)gene and clopidogrel resistance(CR)in Chinese Han patients with ischemic stroke.Methods: A total of 225 patients with ischemic stroke in China were enrolled in this study.After 7 days of treatment with 100 mg aspirin and 75 mg clopidogrel double antibody,the patients were divided into clopidogrel resistance group(CR)and clopidogrel sensitive group(CS)according to the thrombelastography(TEG).The rs141273215 and rs3737224 loci of PEAR1 gene were analyzed by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP).The mutations of PEAR1 gene were detected by electrophoresis and direct sequencing.Construction of haplotypes using SHEsis software.The data were expressed as x ± S,and the data were compared with the independent samples.The data were analyzed by X2 test.Multivariate logistic regression was used to analyze the risk factors.Results:20.9% of patients had clopidogrel resistance,including 47 cases of clopidogrel resistance group and 178 cases of clopidogrel sensitive group.And female,smoking history,drinking history,fasting blood glucose and high density lipoprotein were statistically significant different in the two group.The gene frequency of PEAR1 accorded with Hardy-Weinberg equilibrium law.The rs41273215 CC genotype was more frequent in CR than CS,and CC genotype was more likely to develop clopidogrel resistance than genotype CT + TT(OR = 2.525,95% CI: 1.300-4.905),and the frequency of allele C in CR group was higher than that in CS group(OR = 1.695,95% CI: 1.046-2.746).The correlation between rs3737224 and CR was not found.There was no linkage disequilibrium between the two gene(D ’= 0.28;r2> 0.06)after the analysis of SHEsis software.After multiple factor regression analysis,the rs41273215 CC genotype was an independent risk factor for CR,The incidence of CR in patients with CC genotype was 2.802 times higher than that of shoelaceae CT /TT。Conclusion:The incidence of clopidogrel resistance was 20.9%,and the associated risk factors were male and fasting blood glucose after multivariate regression analysis.And the multivariate analysis found that the CC genotype of the rs141273215 locus of the PEAR1 gene was an independent risk factor for CR in Chinese Han patients with ischemic stroke.