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. CONCLUSION: Our results show for the first time an association of TLR4-(+896 A/G) gene polymorphism with susceptibility to biopsy-proven GCA.
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. CONCLUSION: Our results show for the first time an association of TLR4-(+896 A/G) gene polymorphism with susceptibility to biopsy-proven GCA.
Authors: Mercedes García-Bermúdez; Raquel López-Mejías; Carlos González-Juanatey; Santos Castañeda; José A Miranda-Filloy; Ricardo Blanco; Benjamín Fernández-Gutiérrez; Alejandro Balsa; Isidoro González-Alvaro; Carmen Gómez-Vaquero; Javier Llorca; Javier Martín; Miguel A González-Gay Journal: DNA Cell Biol Date: 2012-02-23 Impact factor: 3.311
Authors: Tanaz A Kermani; Valentin S Schäfer; Cynthia S Crowson; Gene G Hunder; Steven R Ytterberg; Eric L Matteson; Sherine E Gabriel; Kenneth J Warrington Journal: Arthritis Rheum Date: 2010-06
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Authors: Rogelio J Palomino-Morales; Tomas R Vazquez-Rodriguez; Orlando Torres; Inmaculada C Morado; Santos Castañeda; Jose A Miranda-Filloy; Jose L Callejas-Rubio; Benjamin Fernandez-Gutierrez; Miguel A Gonzalez-Gay; Javier Martin Journal: Arthritis Res Ther Date: 2010-03-23 Impact factor: 5.156