title: IL1B and VWF variants are associated with fibrinolytic early recanalization in patients with ischemic stroke.
abstract: OBJECTIVE
  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.
authors.affiliation: Neurovascular Research Laboratory, Institute of Research, Vall d'Hebron Hospital, Pg Vall d'Hebron 119-129, 08035 Barcelona, Spain.
authors.forename: Israel
authors.initials: I
authors.lastname: Fernández-Cadenas
authors.forename: Alberto
authors.initials: A
authors.lastname: Del Río-Espínola
authors.forename: Dolors
authors.initials: D
authors.lastname: Giralt
authors.forename: Sophie
authors.initials: S
authors.lastname: Domingues-Montanari
authors.forename: Adoracion
authors.initials: A
authors.lastname: Quiroga
authors.forename: Maite
authors.initials: M
authors.lastname: Mendióroz
authors.forename: Agustin
authors.initials: A
authors.lastname: Ruíz
authors.forename: Marc
authors.initials: M
authors.lastname: Ribó
authors.forename: Joaquin
authors.initials: J
authors.lastname: Serena
authors.forename: Victor
authors.initials: V
authors.lastname: Obach
authors.forename: Mari Mar
authors.initials: MM
authors.lastname: Freijo
authors.forename: Joan
authors.initials: J
authors.lastname: Martí-Fábregas
authors.forename: Pilar
authors.initials: P
authors.lastname: Delgado
authors.forename: Joan
authors.initials: J
authors.lastname: Montaner
mesh_terms: D000368:Aged; D015331:Cohort Studies; D005260:Female; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011446:Prospective Studies; D012189:Retrospective Studies; D013030:Spain; D020521:Stroke / Q000188:drug therapy* / Q000208:ethnology / Q000235:genetics*; D015912:Thrombolytic Therapy; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D016896:Treatment Outcome; D014841:von Willebrand Factor / Q000235:genetics*
chemical_list: C508585:IL1B protein, human; D053583:Interleukin-1beta; D014841:von Willebrand Factor; D010959:Tissue Plasminogen Activator