Association between toll-like receptor 4 gene polymorphism and biopsy-proven giant cell arteritis.

Authors: Palomino-Morales, R  Torres, O  Vazquez-Rodriguez, TR  Morado, IC  Castaneda, S  Callejas-Rubio, JL  Miranda-Filloy, JA  Fernandez-Gutierrez, B  Martin, J  Gonzalez-Gay, MA 
Citation: Palomino-Morales R, etal., J Rheumatol. 2009 Jul;36(7):1501-6. doi: 10.3899/jrheum.081286. Epub 2009 Jun 16.
Pubmed: (View Article at PubMed) PMID:19531762
DOI: Full-text: DOI:10.3899/jrheum.081286

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.

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CRRD ID: 7777158
Created: 2014-01-06
Species: All species
Last Modified: 2014-01-06
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.