AB0246 Genetic variability with toll-like receptor 10 affects susceptibility to rheumatoid arthritis and modulates response to biological treatment
2018
Background Genetic variability in Toll-like receptor 10 (TLR10) may change the balance between pro- and anti-inflammatory responses, and hence modulate the susceptibility to infection and to autoimmune disease including rheumatoid arthritis (RA). Objectives Therefore we aimed to assess the possible associations of the TLR10 genetic variants with RA susceptibility and/or response to treatment Methods TLR10 gene (rs 11096957, N241H, A>C) polymorphism was genotyped by LightSNiP assay in 303 RA patients (237F/66M) and in 140 healthy individuals from Polish population. Results RA patients with the AC genotype showed predisposition to disease development [OR 1.99 (1.32–3.01); p=0.001], while the AA homozygosity seemed to play a protective role [OR 0.63 (0.42–0.95); p=0.034]. Response to treatment with TNF-alpha inhibitors was more effective after 6 months as compared to 3 months (p=0.001), especially in female patients (p=0.05). Women carrying the A allele responded better to treatment after 6 months of anti-TNF treatment as compared to those with the CC genotype (p=0.053). Response to biological treatment was more effective in patients with low stage of disease (p=0,01), with rheumatoid factor (RF) positivity (p=0.01) and with double positivity against cytrulinated (CCP) protein and RF (p=0.003). RF-positive patients (especially women, p=0.001) characterised with a higher degree of the disease as compared to RF-negative cases (p=0.01). Men had a higher activity of the disease before anti-TNF treatment (p=0.05), therefore the remission of the disease was more common in women (p=0.04). Conclusions These results imply that the TLR10 polymorphism has an important role in RA and may potentially influence risk of the disease and effectiveness of biological treatment. Acknowledgements Supported by the National Science Centre grant No. 2016/ 21/B/NZ5/01901. Disclosure of Interest None declared
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