Confirmation of an IRAK3 polymorphism as a genetic marker predicting response to anti-TNF treatment in rheumatoid arthritis View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2018-01

AUTHORS

J Sode, U Vogel, S Bank, P S Andersen, M L Hetland, H Locht, N H H Heegaard, V Andersen

ABSTRACT

Several genetic variants in Toll-like receptor (TLR) and nuclear factor (NF)-κB signalling pathways have been reported associated with responsiveness to tumour necrosis factor inhibitor (anti-TNF) treatment in rheumatoid arthritis (RA). The present study was undertaken to replicate these findings. In a retrospective case-case study including 1007 Danish anti-TNF-treated RA patients, we genotyped 7 previously reported associated single-nucleotide polymorphisms (SNPs) in these pathways. Furthermore, 5 SNPs previously reported by our group were genotyped in a subcohort (N=469). Primary analyses validated the IRAK3 rs11541076 variant as associated (odds ratio (OR)=1.33, 95% confidence interval (CI): 1.00-1.77, P-value=0.047) with a positive treatment response (EULAR (European League Against Rheumatism) good/moderate vs none response at 4±2 months), and found the NLRP3 rs461266 variant associated (OR=0.75, 95% CI: 0.60-0.94, P=0.014) with a negative treatment response. Meta-analyses combining data from previous studies suggested smaller effect sizes of associations between variant alleles of CHUK rs11591741, NFKBIB rs3136645 and rs9403 and a negative treatment response. In conclusion, this study validates rs11541076 in IRAK3, a negative regulator of TLR signalling, as a predictor of anti-TNF treatment response, and suggests true positive associations of previously reported SNPs within genes encoding activators/inhibitors of NF-κB (CHUK, MYD88, NFKBIB, and NLRP3). More... »

PAGES

81

References to SciGraph publications

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URI

http://scigraph.springernature.com/pub.10.1038/tpj.2016.66

DOI

http://dx.doi.org/10.1038/tpj.2016.66

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1002405188

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/27698401


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