No evidence of major effects in several Toll-like receptor gene polymorphisms in rheumatoid arthritis
1 EA-4222, University of Paris 13, 74 rue Marcel Cachin, 93017 Bobigny cedex, Paris, France
2 Genhotel EA-3886, University Evry-Paris 7 Medical School, Member of the AutoCure European Consortium, CP5727, 91057 Evry-Genopole cedex, Paris, France
3 University of Leipzig, D-04109 Leipzig, Germany
4 Rheumatology Department, Avicenne Hospital AP-HP, 93009 Bobigny cedex, Paris, France
5 Unité de Génétique Clinique, Pôle des Laboratoires Médicaux-Imagerie-Pharmacie, Lariboisière Hospital, AP-HP, 2 rue Ambroise Paré, 75010 Paris, France
Arthritis Research & Therapy 2009, 11:R5 doi:10.1186/ar2589Published: 13 January 2009
The objective was to study the potential genetic contribution of Toll-like receptor (TLR) genes in rheumatoid arthritis (RA). TLRs bind to pathogen-associated molecular patterns, and TLR genes influence both proinflammatory cytokine production and autoimmune responses. Host–pathogen interactions are involved in RA physiopathology.
We tested SNPs of five TLR genes (TLR9, TLR2, TLR6, TLR1, and TLR4) in a cohort of 100 French families with RA. Genotypes were analyzed using the transmission disequilibrium test. As TLR2, TLR6, and TLR1 are located on chromosome 4, we determined the haplotype relative risk. Analyses were performed in subgroups defined by status for rheumatoid factor, anti-cyclic citrullinated peptide autoantibodies, and erosions.
We found no disequilibrium in allele transmission for any of the SNPs of the five TLR genes. In subgroup analyses, no associations were detected linking TLR9, TLR2, or TLR9/TLR2 to rheumatoid factor, anti-cyclic citrullinated peptide autoantibodies, or erosions. Haplotype analysis of the polymorphisms showed no haplotype associations in any of the subgroups.
We found no evidence of major effects of TLR gene polymorphisms in RA, although we tested different TLR phenotypes. Moreover, no associations were noted with autoantibody production or erosions.