Confirmation of an IRAK3 polymorphism as a genetic marker predicting response to anti-TNF treatment in rheumatoid arthritis.
Pharmacogenomics J
; 18(1): 81-86, 2018 01.
Article
en En
| MEDLINE
| ID: mdl-27698401
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).
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Artritis Reumatoide
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Marcadores Genéticos
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Factor de Necrosis Tumoral alfa
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Antirreumáticos
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Polimorfismo de Nucleótido Simple
/
Quinasas Asociadas a Receptores de Interleucina-1
Tipo de estudio:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Pharmacogenomics J
Asunto de la revista:
BIOLOGIA MOLECULAR
/
FARMACOLOGIA
Año:
2018
Tipo del documento:
Article
País de afiliación:
Dinamarca