OBJECTIVE: Toll-like receptors (TLR) have been implicated in the pathogenesis of arthritis. We investigated the role of functional variants of TLR in the disease phenotype and severity of rheumatoid arthritis (RA). METHODS: All patients from a longterm observational inception cohort (n = 319) were genotyped for 22 single-nucleotide polymorphisms (SNP) in TLR2, 3, 4, 5, 7, 8, and 9 using multiplex assays. Clinical characteristics including sex, age at disease onset, rheumatoid factor (RF), and shared epitope positivity and disease activity score and radiological progression were taken into account. Genotypes were analyzed for association with Disease Activity Scores (DAS28) and joint damage (Rau scores) at 3 and 6 years. RESULTS: After Bonferroni correction, there was a moderate association between RF positivity and TLR8-rs5741883. No other TLR variant was significantly associated with any RA clinical characteristics. CONCLUSION: Using a large inception cohort and strict statistical evaluation, we could not identify an association between functional TLR variants and RA phenotype and disease severity. This suggests the functional TLR variants do not play a major role in RA phenotype and disease severity.
OBJECTIVE: Toll-like receptors (TLR) have been implicated in the pathogenesis of arthritis. We investigated the role of functional variants of TLR in the disease phenotype and severity of rheumatoid arthritis (RA). METHODS: All patients from a longterm observational inception cohort (n = 319) were genotyped for 22 single-nucleotide polymorphisms (SNP) in TLR2, 3, 4, 5, 7, 8, and 9 using multiplex assays. Clinical characteristics including sex, age at disease onset, rheumatoid factor (RF), and shared epitope positivity and disease activity score and radiological progression were taken into account. Genotypes were analyzed for association with Disease Activity Scores (DAS28) and joint damage (Rau scores) at 3 and 6 years. RESULTS: After Bonferroni correction, there was a moderate association between RF positivity and TLR8-rs5741883. No other TLR variant was significantly associated with any RA clinical characteristics. CONCLUSION: Using a large inception cohort and strict statistical evaluation, we could not identify an association between functional TLR variants and RA phenotype and disease severity. This suggests the functional TLR variants do not play a major role in RA phenotype and disease severity.
Authors: Marieke J H Coenen; Christian Enevold; Pilar Barrera; Mascha M V A P Schijvenaars; Erik J M Toonen; Hans Scheffer; Leonid Padyukov; Alf Kastbom; Lars Klareskog; Anne Barton; Wietske Kievit; Maarten J Rood; Tim L Jansen; Dorine Swinkels; Piet L C M van Riel; Barbara Franke; Klaus Bendtzen; Timothy R D J Radstake Journal: PLoS One Date: 2010-12-15 Impact factor: 3.240
Authors: Magdalena J Laska; Bettina Hansen; Anne Troldborg; Tove Lorenzen; Kristian Stengaard-Pedersen; Peter Junker; Bjørn A Nexø; Hanne M Lindegaard Journal: BMC Res Notes Date: 2014-10-10