Association between anti-tumour necrosis factor treatment response and genetic variants within the TLR and NFκB signalling pathways

Catherine Potter, Heather J. Cordell, Anne Barton, Ann K. Daly, Kimme L. Hyrich, Derek A. Mann, Ann W. Morgan, Anthony G. Wilson, John D. Isaacs

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Objective: To determine whether genetic variation within genes integral to the Toll-like receptor (TLR) and NFκB signalling systems, two cardinal regulators of inflammatory and immune responses, contributes towards the observed variation in response to tumour necrosis factor (TNF) blocking agents in patients with rheumatoid arthritis (RA). Methods: Pairwise-tagging single nucleotide polymorphisms (SNPs) spanning 24 candidate genes were selected and genotyped in a large UK cohort of patients receiving anti-TNF therapy for RA. Multivariate regression analyses were performed to test association between individual genotypes, under an additive model, and treatment response at 6 months' follow-up assessed using both the absolute change in 28-joint count Disease Activity Score (DAS28) and the European League Against Rheumatism (EULAR) response criteria. Analyses were performed across subgroups comprising etanercept-, infliximab- and infliximab/adalimumab-treated patients as well as the combined anti-TNF-treated cohort. p Values
    Original languageEnglish
    Pages (from-to)1315-1320
    Number of pages5
    JournalAnnals of the rheumatic diseases
    Volume69
    Issue number7
    DOIs
    Publication statusPublished - Jul 2010

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