title: Brain arteriovenous malformations are associated with interleukin-1 cluster gene polymorphisms.
abstract: BACKGROUND
  Brain arteriovenous malformations (BAVMs) are a rare but important cause of hemorrhagic stroke in young adults. Functional polymorphisms in proinflammatory cytokines have been associated with various cerebrovascular phenotypes, including ischemic stroke, aneurysmal subarachnoid hemorrhage, and BAVM.
  
  
  OBJECTIVE
  To investigate whether functional polymorphisms in the IL-1α, IL-1β, and IL-1RN genes are associated with both susceptibility and clinical characteristics in BAVM patients.
  
  
  METHODS
  Allelic and genotypic frequencies of IL-1α (-889 C>T), IL-1β (-511 C>T), and IL-1RN (VNTR) polymorphisms were analyzed in 101 unrelated BAVM patients and in 210 healthy subjects. Main clinical characteristics of the disease were compared according to different genotypes.
  
  
  RESULTS
  Both allelic and genotypic frequencies of IL-1α -889 C>T showed a significant association with BAVM (P < .001). The carriage of the T allele was related to a 2.47 increased risk of BAVM (odds ratio, 2.47; 95% confidence interval: 1.72-3.56). Allelic and genotypic frequencies of IL-1RN VNTR were different between cases and controls (P = .009). Allele 1 was associated with about a twofold increased disease risk (95% confidence interval: 2.01-5.58). Haplotype analyses confirmed these findings. Several clinical characteristics of the disease were significantly modified by IL-1α and IL-1β genotypes.
  
  
  CONCLUSIONS
  Our data suggest that functional polymorphisms within the IL-1 complex gene are associated with BAVMs and influence the clinical characteristics of the disease, supporting a role for proinflammatory cytokines in disease etiopathogenesis.
authors.affiliation: Division of Neurosurgery, Department of Neuroscience, University of Torino, Torino, Italy. marco.fontanella@tin.it
authors.forename: Marco
authors.initials: M
authors.lastname: Fontanella
authors.forename: Elisa
authors.initials: E
authors.lastname: Rubino
authors.forename: Emanuela
authors.initials: E
authors.lastname: Crobeddu
authors.forename: Salvatore
authors.initials: S
authors.lastname: Gallone
authors.forename: Salvatore
authors.initials: S
authors.lastname: Gentile
authors.forename: Diego
authors.initials: D
authors.lastname: Garbossa
authors.forename: Alessandro
authors.initials: A
authors.lastname: Ducati
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Pinessi
authors.forename: Innocenzo
authors.initials: I
authors.lastname: Rainero
mesh_terms: D000328:Adult; D001164:Arteriovenous Fistula / Q000150:complications / Q000235:genetics*; D016000:Cluster Analysis; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics; D007375:Interleukin-1 / Q000235:genetics*; D053582:Interleukin-1alpha / Q000235:genetics; D053583:Interleukin-1beta / Q000235:genetics; D002538:Intracranial Arteriovenous Malformations / Q000150:complications / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*
chemical_list: C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D053582:Interleukin-1alpha; D053583:Interleukin-1beta