title: TLR-4 and VEGF polymorphisms in chronic periaortitis.
abstract: OBJECTIVE
  Chronic periaortitis (CP) is a rare disease that is characterised by fibro-inflammatory tissue surrounding the abdominal aorta and has both non-aneurysmal (idiopathic retroperitoneal fibrosis [IRF]) and aneurysmal forms (inflammatory abdominal aortic aneurysm [IAAA]). We investigated whether toll-like receptor 4 (TLR-4) and vascular endothelial growth factor (VEGF) polymorphisms were associated with susceptibility to, and the clinical features of CP.
  
  
  METHODS
  One hundred and two CP patients and 200 healthy controls were molecularly genotyped for TLR-4 gene polymorphism (+896 A/G) (rs4986790), VEGF mutations +936 C/T (rs3025039) and -634 C/G (rs2010963), and an 18 base pair (bp) insertion/deletion (I/D) polymorphism at -2549 of the VEGF promoter region. The patients were grouped on the basis of the type of CP (IRF or IAAA), and the presence or absence of established atherosclerotic disease (ischemic heart disease, cerebrovascular disease, and peripheral arterial disease).
  
  
  RESULTS
  There were no significant differences in the distribution of the studied polymorphisms between the patients and controls. However, carriage of the +936 T allele was significantly more frequent in the patients with IRF than in those with IAAA (26.5% vs 5.3%; p = 0.046; OR 6.49 [95% CI 0.82-51.54]). There were significantly more carriers of the I allele among the patients with ureteral obstruction (83.8% vs 58.8%; p = 0.006; OR 3.63 [95% CI 1.42-9.28]) and those who received conservative treatment (48.5% vs 23.5%; p = 0.015; OR 3.06 [95% CI 1.22-7.721]) than among those without, and II homozygosity was significantly more frequent in the patients with deep vein thrombosis than in those without (30.4% vs 11.7%, p = 0.031; OR 3.31 [95% CI 1.07-10.21]).
  
  
  CONCLUSIONS
  The VEGF +936 C/T polymorphism may be associated with an increased risk of developing the non-aneurysmal IRF form of CP. Carriers of the I allele and II homozygosity are respectively at increased risk of developing ureteral obstruction and deep vein thrombosis.
authors.affiliation: Rheumatology Unit, L. Sacco University Hospital of Milan, Milan, Italy.
authors.forename: Fabiola
authors.initials: F
authors.lastname: Atzeni
authors.forename: Luigi
authors.initials: L
authors.lastname: Boiardi
authors.forename: Augusto
authors.initials: A
authors.lastname: Vaglio
authors.forename: Davide
authors.initials: D
authors.lastname: Nicoli
authors.forename: Enrico
authors.initials: E
authors.lastname: Farnetti
authors.forename: Alessandra
authors.initials: A
authors.lastname: Palmisano
authors.forename: Nicolò
authors.initials: N
authors.lastname: Pipitone
authors.forename: Davide
authors.initials: D
authors.lastname: Martorana
authors.forename: Gabriella
authors.initials: G
authors.lastname: Moroni
authors.forename: Selena
authors.initials: S
authors.lastname: Longhi
authors.forename: Francesco
authors.initials: F
authors.lastname: Bonatti
authors.forename: Carlo
authors.initials: C
authors.lastname: Buzio
authors.forename: Carlo
authors.initials: C
authors.lastname: Salvarani
mesh_terms: D000483:Alleles; D050197:Atherosclerosis / Q000150:complications / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D012185:Retroperitoneal Fibrosis / Q000150:complications / Q000235:genetics*; D051197:Toll-Like Receptor 4 / Q000235:genetics*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D042461:Vascular Endothelial Growth Factor A