title: CD40-1C>T polymorphism (rs1883832) is associated with brain vessel reocclusion after fibrinolysis in ischemic stroke.
abstract: OBJECTIVE
  To find genetic predictors of reocclusion after successful fibrinolytic therapy during the acute phase of ischemic stroke.
  
  
  METHODS
  This was a case-case prospective study analyzing 236 polymorphisms in a cohort of 222 patients treated with tissue plasminogen activator, from which 16 patients suffered a reocclusion event (7.2%). A predictive scale was generated using independent polymorphisms with a dominant/recessive model and tandem occlusion, weighted by their beta-coefficients in logistic regression.
  
  
  RESULTS
  Using a dominant/recessive model, the rs1800801 SNP from the MGP gene (odds ratio [OR]: 15.25; 95% CI: 2.23-104.46; adjusted p = 0.006) and the rs1883832 SNP from CD40 gene (OR: 0.077; 95% CI: 0.009-0.66; adjusted p = 0.019) were independently associated with reocclusion after logistic regression adjustment by clinical predictors. In an additive model, only the rs1883832 SNP (OR: 4.43; 95% CI: 1.62-12.15; adjusted p = 0.004) was related to reocclusion occurrence. The predictive model that was generated stratified the reocclusion risk from less than 1% to more than 70%. Reocclusions were associated with neurological worsening at 24 h (patients with reocclusion: 26.7%, versus patients without reocclusion: 4.9%; p = 0.002), as it was seen for MGP -7A>G (AA: 17.2% vs AG+GG: 4.5%; p = 0.027), but not for CD40 1C>T (CC: 4.5% vs CT+TT: 7.7%; p = 0.565). There was an association between CD40 -1C>T genotype and CD40 transcriptional activity in peripheral blood mononuclear cells (median expression values TT: 65.75%, CT: 70.80%, CC: 96.00%; p = 0.023). However, CD40 soluble fraction was not a useful biomarker of reocclusion status.
  
  
  CONCLUSIONS
  An association was found between MGP -7A>G and CD40 -1C>T polymorphisms, and reocclusion risk. The predictive scale that was generated permits the stratification of patients by their reocclusion risk with higher accuracy than clinical parameters alone.
authors.affiliation: Neurovascular Research Laboratory, Institut de Recerca, Hospital Vall d'Hebron, Pg Vall d'Hebron 119-129, 08035, Barcelona, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: del Río-Espínola
authors.forename: Israel
authors.initials: I
authors.lastname: Fernández-Cadenas
authors.forename: Marta
authors.initials: M
authors.lastname: Rubiera
authors.forename: Manuel
authors.initials: M
authors.lastname: Quintana
authors.forename: Sophie
authors.initials: S
authors.lastname: Domingues-Montanari
authors.forename: Maite
authors.initials: M
authors.lastname: Mendióroz
authors.forename: Jessica
authors.initials: J
authors.lastname: Fernández-Morales
authors.forename: Dolors
authors.initials: D
authors.lastname: Giralt
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Molina
authors.forename: José
authors.initials: J
authors.lastname: Alvarez-Sabín
authors.forename: Joan
authors.initials: J
authors.lastname: Montaner
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D015415:Biomarkers / Q000097:blood; D001921:Brain / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D002545:Brain Ischemia / Q000150:complications / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000235:genetics*; D002135:Calcium-Binding Proteins / Q000235:genetics; D002339:Carotid Arteries / Q000000981:diagnostic imaging; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D011446:Prospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012306:Risk; D020521:Stroke / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D048008:TNF Receptor-Associated Factor 3 / Q000097:blood / Q000235:genetics*; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome; D018608:Ultrasonography, Doppler; D000097568:Matrix Gla Protein
chemical_list: D015415:Biomarkers; D002135:Calcium-Binding Proteins; D016326:Extracellular Matrix Proteins; D005343:Fibrinolytic Agents; D048008:TNF Receptor-Associated Factor 3; D010959:Tissue Plasminogen Activator; D000097568:Matrix Gla Protein; C090656:TRAF3 protein, human