Association between toll-like receptor 4 gene polymorphism and biopsy-proven giant cell arteritis.
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.
Palomino-Morales
Rogelio
R
Instituto de Parasitología y Biomedicina López Neyra, Consejo Superior de Investigaciones Cientificas (CSIC), Granada, Spain.
Torres
Orlando
O
Vazquez-Rodriguez
Tomas R
TR
Morado
Inmaculada C
IC
Castañeda
Santos
S
Callejas-Rubio
Jose L
JL
Miranda-Filloy
Jose A
JA
Fernandez-Gutierrez
Benjamin
B
Martin
Javier
J
Gonzalez-Gay
Miguel A
MA
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*
C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4