title: Association between toll-like receptor 4 gene polymorphism and biopsy-proven giant cell arteritis.
abstract: OBJECTIVE
  Dendritic cells localized at the adventitia-media border of the normal medium-sized arteries play a pivotal role in the initiation of giant cell arteritis (GCA). These cells express a singular surface receptor profile, including a series of Toll-like receptors (TLR). Ligands of TLR-4 promote activation and differentiation of adventitial dendritic cells and are directly implicated in the pathogenesis of GCA. We aimed to assess the potential implication of the TLR4-(+896 A/G) gene polymorphism in the susceptibility to GCA.
  
  
  METHODS
  A total of 210 patients diagnosed with biopsy-proven GCA and 678 matched controls were included in our study. DNA from patients and controls was obtained from peripheral blood. Samples were genotyped for the TLR4-(+896 A/G) (rs4986790) gene polymorphism by polymerase chain reaction, using a predesigned TaqMan allele discrimination assay.
  
  
  RESULTS
  The TLR4 +896 G allele was significantly increased in biopsy-proven GCA patients compared to controls [p = 0.01; odds ratio (OR) 1.65; 95% confidence interval (CI) 1.08-2.52]. The increase was due to a significantly increased frequency of heterozygosity for the TLR4 -896 A/G genotype in the group of patients with biopsy-proven GCA compared to controls (TLR4 -896 A/G heterozygous in patients with GCA 18.1% compared to 11.4% in controls: p = 0.01; OR 1.72; 95% CI 1.10-2.69). However, no significant differences were observed when patients with GCA were stratified according to the presence of specific clinical features of the disease.
  
  
  CONCLUSIONS
  Our results show for the first time an association of TLR4-(+896 A/G) gene polymorphism with susceptibility to biopsy-proven GCA.
authors.affiliation: Instituto de Parasitología y Biomedicina López Neyra, Consejo Superior de Investigaciones Cientificas (CSIC), Granada, Spain.
authors.forename: Rogelio
authors.initials: R
authors.lastname: Palomino-Morales
authors.forename: Orlando
authors.initials: O
authors.lastname: Torres
authors.forename: Tomas R
authors.initials: TR
authors.lastname: Vazquez-Rodriguez
authors.forename: Inmaculada C
authors.initials: IC
authors.lastname: Morado
authors.forename: Santos
authors.initials: S
authors.lastname: Castañeda
authors.forename: Jose L
authors.initials: JL
authors.lastname: Callejas-Rubio
authors.forename: Jose A
authors.initials: JA
authors.lastname: Miranda-Filloy
authors.forename: Benjamin
authors.initials: B
authors.lastname: Fernandez-Gutierrez
authors.forename: Javier
authors.initials: J
authors.lastname: Martin
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Gonzalez-Gay
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001706:Biopsy; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D013700:Giant Cell Arteritis / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D051197:Toll-Like Receptor 4 / Q000235:genetics*
chemical_list: C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4