title: Association of the R92Q TNFRSF1A mutation and extracranial deep vein thrombosis in patients with Behçet's disease.
abstract: OBJECTIVE
  Behçet's disease is a chronic, relapsing, multisystemic inflammatory disorder characterized by recurrent oral and genital ulcers and by ocular, articular, vascular, and central nervous system involvement. The tumor necrosis factor alpha (TNFalpha) pathway is likely involved in the pathophysiology of Behçet's disease. One of the 2 TNFalpha receptors is TNF receptor superfamily 1A (TNFRSF1A). We searched for R92Q TNFRSF1A mutations in patients with Behçet's disease.
  
  
  METHODS
  A search for TNFRSF1A mutations was performed by polymerase chain reaction amplification of the TNFRSF1A gene, followed by denaturing high-performance liquid chromatography scanning.
  
  
  RESULTS
  Among the 74 unrelated European patients with Behçet's disease, 5 (6.8%) carried the R92Q TNFRSF1A mutation. The frequency of the R92Q mutation in patients with Behçet's disease was significantly higher than that in controls (P = 0.006 by Fisher's exact test). Deep vein thrombosis was significantly associated with the R92Q mutation (P = 0.001 [with Bonferroni adjustment for multiple comparisons]). Among the 30 patients with thrombosis, 10 had cerebral thrombophlebitis. None of these patients had the R92Q mutation. Among the 20 patients with Behçet's disease who had extracranial deep vein thrombosis, 6 had the R92Q mutation, whereas 14 did not (P < 0.0001)
  
  
  CONCLUSIONS
  The R92Q mutation in patients with Behçet's disease is associated with an increased risk of extracranial venous thrombosis. This new finding may help in understanding the complex prothrombotic state in patients with Behçet's disease.
authors.affiliation: Hôpital Pitié-Salpêtrière, Paris, France. zahir.amoura@psl.ap-hop-paris.fr <zahir.amoura@psl.ap-hop-paris.fr>
authors.forename: Zahir
authors.initials: Z
authors.lastname: Amoura
authors.forename: Catherine
authors.initials: C
authors.lastname: Dodé
authors.forename: Sophie
authors.initials: S
authors.lastname: Hue
authors.forename: Sophie
authors.initials: S
authors.lastname: Caillat-Zucman
authors.forename: Seiamak
authors.initials: S
authors.lastname: Bahram
authors.forename: Marc
authors.initials: M
authors.lastname: Delpech
authors.forename: Gilles
authors.initials: G
authors.lastname: Grateau
authors.forename: Bertrand
authors.initials: B
authors.lastname: Wechsler
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Piette
mesh_terms: D001528:Behcet Syndrome / Q000150:complications*; D005260:Female; D005784:Gene Amplification; D006801:Humans; D008297:Male; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics*; D020246:Venous Thrombosis / Q000209:etiology / Q000235:genetics*
chemical_list: D047888:Receptors, Tumor Necrosis Factor, Type I