VASP Phosphorylation And Genetic Polymorphism In Non-cardioemb-olic Ischemic Stroke Patients With Clopidogrel Resistance

Objective: The relationship between VASP phosphorylation, CYP2C19,CYP3A4genetic polymorphism and non-cardioembolic ischemic stroke (NCIS) patients with CR isstudied, which identify the patients with CR from biological and genetical characteristcs,so that make the conversion of basic research to clinical medicine.Methods：A total of95patients with acute NCIS were enrolled in this study. Weanalysed the degree of VASP phosphorylation by flow cytometry to measure the baselineplatelet reactivity index（BPRI）and post-treatment platelet reactivity index(PPRI) after7days, and defined the PPRI≥50%as laboratory clopidogrel resistance (LCR). We testthe CYP2C19*2（681G>A）,CYP2C19*3(636G>A),CYP3A4(IVS10+12G>A)andCYP3A4(IVS7+894C>T)genotype by Chain Termination Method. Recording clinical dataand follow-up for6months, we defined clinical clopidogrel resistance（CCR）that patientsoccurred stroke in progression（NIHSS score increased≥2）during hospitalization oroccurred recurrent ischemic stroke or other ischemic vascular events in the follow-upperiod.Results：（1）The LCR was41.05%in our study, gene CYP2C19(681G>A),CYP2C19(636G>A) and CYP3A4(IVS10+12G>A) variant genotypes GA/AA ratioswere as follows:15.79%,38.95%and40.00%, CYP3A4(IVS7+894C>T) variantgenotype CT/TT ratio was33.68%. There are18(18.95%) patients with CCR for the6-months follow-up（.2）The variant genotypes GA/AA of CYP2C19（681G>A）existLCR significantly higher than the wild-type gene(χ2=11.16,P=0.001), The same as theCYP2C19(636G>A) gene (χ2=4.829,P=0.028). The CYP2C19(681G>A)(OR:6.272，95%CI2.162,18.199P=0.001)and CYP2C19(636G>A)(OR5.625,95%CI1.439,21.583,P=0.013) polymorphisms were risk factors of LCR.（3）Patients with LCR possibility ofoccurrence CCR were significantly higher than patients with non-LCR （χ2=4.844,P=0.028）. The variant genotypes GA/AA of CYP2C19（681G>A）exist CCRsignificantly higher than the wild-type gene（χ2=10.341,P=0.001).The CYP2C19(681G>A) (OR7.814，95%CI1.816,33.618P=0.006), LCR（OR5.881，95%CI1.373,25.192，P=0.017) and Essen score (OR8.351，95%CI1.848,37.745P=0.006) were risk factorsof CCR.Conclusions: Patients with the CYP2C19（636G>A，681G>A）polymorphism havesignificantly increased LCR compared with patients with the wild-type. LCR andCYP2C19polymorphisms was significantly correlated to clinical outcomes in patientswith NCIS taking clopidogrel, so that LCR and CYP2C19polymorphisms test in clinicalpractice may be considered.