IL1B and VWF variants are associated with fibrinolytic early recanalization in patients with ischemic stroke

Stroke. 2012 Oct;43(10):2659-65. doi: 10.1161/STROKEAHA.112.657007. Epub 2012 Aug 2.


Background and purpose: There is a great interindividual variability among patients with acute ischemic stroke regarding the response to intravenous tissue-type plasminogen activator treatment. The aim of this study was to identify genetic variants associated with recanalization, and thus treatment efficacy, after tissue-type plasminogen activator administration.

Methods: A total of 140 single nucleotide polymorphisms from 97 candidate genes were successfully genotyped by SNPlex in 2 cohorts, accounting for 497 prospectively recruited tissue-type plasminogen activator-treated patients, of whom 33% recanalized during tissue-type plasminogen activator infusion. Functional studies were then performed, including assessment of interleukin 1B mRNA levels and von Willebrand factor, FIII, FVII, FVIII, and FX protein activity.

Results: After replication, the following single nucleotide polymorphisms were associated with early recanalization: rs1143627 in IL1B gene (CC: 53.1% of recanalization, A-carriers: 32.7%; P=0.022; replication cohort: P=0.046), rs16944 in IL1B gene (AA: 50% of recanalization, G-carriers: 32%; P=0.038; replication cohort: P=0.049), and rs1063856 in the vWF gene (GG: 53.8% of recanalization, A-carriers: 31.5%; P=0.006; replication cohort: P=0.046). The functional studies revealed an association between the rs1063856 single nucleotide polymorphisms in vWF and FVIII activity (AA: 115.93%, AG: 156.07%, GG: 83.42%; P=0.005).

Conclusions: Three single nucleotide polymorphisms were associated with tissue-type plasminogen activator efficacy in the Spanish population, and their mechanism of action might be associated with the activity of coagulation factors.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cohort Studies
  • Female
  • Genetic Testing
  • Genotype
  • Humans
  • Interleukin-1beta / genetics*
  • Logistic Models
  • Male
  • Pharmacogenetics
  • Polymorphism, Single Nucleotide / genetics*
  • Prospective Studies
  • Retrospective Studies
  • Spain
  • Stroke / drug therapy*
  • Stroke / ethnology
  • Stroke / genetics*
  • Thrombolytic Therapy*
  • Tissue Plasminogen Activator / therapeutic use*
  • Treatment Outcome
  • von Willebrand Factor / genetics*


  • IL1B protein, human
  • Interleukin-1beta
  • von Willebrand Factor
  • Tissue Plasminogen Activator