title: VASP phosphorylation and genetic polymorphism for clopidogrel resistance in Chinese patients with non-cardioembolic ischemic stroke.
abstract: BACKGROUND
  Clopidogrel 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.
  
  
  METHODS
  A 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 7 days 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 6 months.
  
  
  RESULTS
  The 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.
  
  
  CONCLUSIONS
  In clinical practice,LCR and CYP2C19 gene polymorphism should be assessed in NCIS patients receiving clopidogrel treatment.
authors.affiliation: The First Affiliated Hospital, Jinan University, Guangzhou, 510632, China.
authors.forename: Shijun
authors.initials: S
authors.lastname: Zhang
authors.forename: Xinqiang
authors.initials: X
authors.lastname: Lai
authors.forename: Wenxian
authors.initials: W
authors.lastname: Li
authors.forename: Zhilin
authors.initials: Z
authors.lastname: Xiong
authors.forename: Anding
authors.initials: A
authors.lastname: Xu
authors.forename: Anding
authors.initials: A
authors.lastname: Xu
authors.forename: Li'an
authors.initials: L
authors.lastname: Huang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002545:Brain Ischemia / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D002681:China / Q000453:epidemiology; D000077144:Clopidogrel; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015995:Prevalence; D015203:Reproducibility of Results; D012307:Risk Factors; D012680:Sensitivity and Specificity; D020521:Stroke / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D017211:Treatment Failure; D055815:Young Adult; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D015815:Cell Adhesion Molecules; D005819:Genetic Markers; D008840:Microfilament Proteins; D010750:Phosphoproteins; D010975:Platelet Aggregation Inhibitors; D000098662:Vasodilator-Stimulated Phosphoprotein; D000077144:Clopidogrel; D013988:Ticlopidine