Association Between Toll-like Receptor 4 Gene Polymorphism and Biopsy-proven Giant Cell Arteritis

• Published in: Journal of rheumatology Vol. 36; no. 7; pp. 1501 - 1506
• Main Authors: PALOMINO-MORALES, Rogelio, TORRES, Orlando, VAZQUEZ-RODRIGUEZ, Tomas R, MORADO, Inmaculada C, CASTANEDA, Santos, CALLEJAS-RUBIO, Jose L, MIRANDA-FILLOY, Jose A, FERNANDEZ-GUTIERREZ, Benjamin, MARTIN, Javier, GONZALEZ-GAY, Miguel A
• Format: Journal Article
• Language: English
• Published: Toronto, ON The Journal of Rheumatology 01-07-2009; Journal of Rheumatology Publishing
• Subjects: Aged; Aged, 80 and over; Alleles; Biological and medical sciences; Biopsy; Case-Control Studies; Diseases of the osteoarticular system; Female; Genetic Predisposition to Disease - genetics; Genotype; Giant Cell Arteritis - diagnosis; Giant Cell Arteritis - genetics; Giant Cell Arteritis - pathology; Humans; Male; Medical sciences; Middle Aged; Polymorphism, Genetic - genetics; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Toll-Like Receptor 4 - genetics; Toll like receptor 4; GENETIC STUDIES; Rheumatology; Cardiovascular disease; GENE POLYMORPHISM; Vascular disease; Vasculitis; TOLL-LIKE RECEPTOR-4; Biopsy; Systemic disease; Genetics; Giant cell arteritis; Polymorphism; DISEASE SUSCEPTIBILITY
• ISSN: 0315-162X; 1499-2752
• 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.