Toll-like receptor 4 gene polymorphisms in polymyalgia rheumatica and elderly-onset rheumatoid arthritis

Coding variants in TLR4 gene have been reported to be associated with inflammatory diseases. The aim of this study was to determine whether two of these polymorphisms (Asp299Gly and Thr399Ile) of TLR4 contribute to the genetic background of polymyalgia rheumatica (PMR) and elderly-onset rheumatoid a...

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Bibliographic Details
Published in:Clinical and experimental rheumatology 2011-09, Vol.29 (5), p.795-800
Main Authors: ALVAREZ-RODRIGUEZ, L, LOPEZ-HOYOS, M, BEARES, I, MATA, C, GARCIA-UNZUETA, M, CALVO ALEN, J, BLANCO, R, AURRECOECHEA, E, TRIPATHI, G, MARTINEZ-TABOADA, V. M
Format: Article
Language:English
Subjects:
Age of Onset
Aged
Aged, 80 and over
Arthritis, Rheumatoid - genetics
Arthritis, Rheumatoid - immunology
Biological and medical sciences
Diseases of the osteoarticular system
Female
Gene Frequency
Genetic Predisposition to Disease - genetics
Haplotypes
Humans
Inflammatory joint diseases
Male
Medical sciences
Middle Aged
Polymorphism, Genetic - genetics
Polymyalgia Rheumatica - genetics
Polymyalgia Rheumatica - immunology
Toll-Like Receptor 4 - genetics
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Summary:Coding variants in TLR4 gene have been reported to be associated with inflammatory diseases. The aim of this study was to determine whether two of these polymorphisms (Asp299Gly and Thr399Ile) of TLR4 contribute to the genetic background of polymyalgia rheumatica (PMR) and elderly-onset rheumatoid arthritis (EORA). Furthermore, we have attempted to correlate the functional consequences of these polymorphisms. 164 patients with PMR, 93 with EORA and 126 unrelated age-matched controls were genotyped. The TLR4 genotypes were determined using allele-specific primers and restriction fragment length polymorphism analysis. Association of genotypes and alleles with disease susceptibility and disease phenotypes were studied. TLR4 expression was assessed on PBMCs by flow cytometry and TLR4 function was assessed by stimulating PBMCs in vitro with LPS. No significant difference in allele frequency or genotype between patients with elderly-onset inflammatory conditions and controls was observed. The Thr399Ile CC genotype was associated with a higher cumulative dose of corticosteroids in patients with PMR (p=0.031). We found no association with TLR4 expression on B cells, T cells or monocytes or a distinct phenotype of TLR4 response with the Asp299Gly or Thr399Ile genotypes. These results do not support the association of these TLR4 variants with two age-related inflammatory conditions. The value of determining Thr399Ile genotypes for disease prognosis in PMR should be confirmed in different populations.
ISSN:0392-856X
1593-098X