VASP phosphorylation and genetic polymorphism for clopidogrel resistance in Chinese patients with non-cardioembolic ischemic stroke

Abstract

BackgroundClopidogrel resistance(CR)is found in non-cardioembolic ischemic stroke (NCIS) patients. However, it is still largely unknown how to identify CR in NCIS patients by laboratory and genetic characteristics. MethodsA total of 95 patients with acute NCIS were recruited. Phosphorylation of the vasodilator stimulated phosphoprotein (VASP) was detected using flow cytometry, and genes(CYP2C19,CYP3A4) were detected using the Sanger method. The baseline of platelet reactivity index (BPRI) before clopidogrel treatment and the platelet reactivity index with clopidogrel treatment (CPRI) for 7days were measured. Laboratory clopidogrel resistance (LCR) was defined as CPRI of ≥50%.Clinical clopidogrel resistance (CCR) was defined as the presence of progressive stroke during hospitalization, stroke recurrence or occurrence of other ischemic vascular events within 6months. ResultsThe incidence of LCR was 41.05% and 18.95% developed CCR. The incidence of LCR was significantly higher in GA/AA patients with CYP2C19 (681G>A) (χ2=11.16, P=0.001) and CYP2C19 (636G>A) (χ2=4.829, P=0.028) than in wildtype GG patients. CYP2C19 (681G>A) (OR 6.272, 95%CI 2.162,18.199,P=0.001) and CYP2C19 (636G>A) (OR: 5.625,95%CI 1.439, 21.583,P=0.013) were risk factors for LCR. patients with LCR were more likely to develop CCR (χ2=6.021, P=0.014). The probability of CCR was markedly increased in GA/AA patients with CYP2C19 (681G>A) (χ2=10.341, P=0.001). We identified CYP2C19 (681G>A) (OR 7.814, 95%CI 1.816, 33.618 P=0.006), Essen score (OR 8.351, 95%CI 1.848, 37.745 P=0.006), and LCR (OR 5.881, 95%CI 1.373, 25.192, P=0.017) as risk factors for CCR. ConclusionIn clinical practice,LCR and CYP2C19 gene polymorphism should be assessed in NCIS patients receiving clopidogrel treatment.The Chinese Clinical Trial Registry number: ChiCTR-ONC-13003406