English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Plus monthly

Global: Zendy Tools annual

Global: Zendy Tools monthly

Global: Zendy Free Plan

Objectives  To determine whether genetic variation within genes related to the Toll-like receptor, inflammasome and interferon-γ pathways contributes to the differences in treatment response to tumour necrosis factor inhibitors (anti-TNF) in patients with rheumatoid arthritis (RA).    Methods  In a retrospective case-case study, we assessed 23 functional single nucleotide polymorphisms (SNPs) in 15 genes. We included 538 anti-TNF naïve Danish RA patients from the nationwide DANBIO database. Multivariable logistic regression analyses were performed to detect associations (p-value<0.05) between genotypes and European League Against Rheumatism (EULAR) treatment responses. False Discovery Rate corrections for multiple testing (q-value) and stratified analyses were performed to investigate association with individual therapies and IgM-rheumatoid factor (RF) status.    Results  Six of twenty successfully genotyped polymorphisms were nominally associated with EULAR treatment response. Three of these were in weak to moderate linkage disequilibrium with polymorphisms previously reported associated with anti-TNF treatment response.  TLR5 (rs5744174) variant allele carriers (odds ratio(OR) = 1.7(1.1–2.5),p = 0.010,q = 0.46) and  TLR1 (rs4833095) homozygous variant carriers (OR = 2.8(1.1–7.4),p = 0.037,q = 0.46) had higher odds for a positive treatment response.  NLRP3 (rs10754558) variant allele carriers (odds ratio(OR) = 0.6(0.4–1.0),p = 0.045,q = 0.46) were more likely to have a negative treatment response.  The association in  TLR5 (rs5744174) remained significant after correction for multiple comparisons among patients negative for RF (OR = 6.2(2.4–16.3),p = 0.0002,q = 0.024). No other association withstood correction for multiple testing. Post hoc analyses showed that change in Patient Global score on a visual analogue scale (VAS) and change in pain VAS were the main factors responsible for the association.    Conclusions  We reproduced previously reported associations between genetic variation in the  TLR10/1/6  gene cluster,  TLR5 , and  NLRP3  loci and response to anti-TNF treatment in RA. Changes in VAS pain and patient global scores were the main contributors to the association found for  TLR5 . Furthermore, we identified other candidate genes that require replication in independent cohorts.

Genetic Variations in Pattern Recognition Receptor Loci Are Associated with Anti-TNF Response in Patients with Rheumatoid Arthritis