No evidence of major effects in several Toll-like receptor gene polymorphisms in rheumatoid arthritis.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Jaen
Olivier
O
EA-4222, University of Paris 13, Bobigny Cedex, Paris, France. olivier.jaen@club-internet.fr
Petit-Teixeira
Elisabeth
E
Kirsten
Holger
H
Ahnert
Peter
P
Semerano
Luca
L
Pierlot
Céline
C
Cornelis
Francois
F
Boissier
Marie-Christophe
MC
Falgarone
Geraldine
G
D000328:Adult; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D051193:Toll-Like Receptors / Q000235:genetics*
D051193:Toll-Like Receptors