PT - JOURNAL ARTICLE AU - Rogelio Palomino-Morales AU - Orlando Torres AU - Tomas R. Vazquez-Rodriguez AU - Inmaculada C. Morado AU - Santos Castañeda AU - Jose L. Callejas-Rubio AU - Jose A. Miranda-Filloy AU - Benjamin Fernandez-Gutierrez AU - Javier Martin AU - Miguel A. Gonzalez-Gay TI - Association Between Toll-like Receptor 4 Gene Polymorphism and Biopsy-proven Giant Cell Arteritis AID - 10.3899/jrheum.081286 DP - 2009 Jun 16 TA - The Journal of Rheumatology 4099 - http://www.jrheum.org/content/early/2009/06/15/jrheum.081286.short 4100 - http://www.jrheum.org/content/early/2009/06/15/jrheum.081286.full AB - 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 GCAand 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.