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Polymorphisms within Genes Involved in Regulation of the NF-κB Pathway in Patients with Rheumatoid Arthritis

Genes involved in regulation of the nuclear factor-κB (NF-κB)—pathway are suggested to play a role in pathogenesis of rheumatoid arthritis (RA). In the present study, genetic polymorphisms of TLR2, TLR4, TLR9 and NF-κB1 genes were investigated to assess their associations with RA susceptibility, pro...

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Autores principales: Gębura, Katarzyna, Świerkot, Jerzy, Wysoczańska, Barbara, Korman, Lucyna, Nowak, Beata, Wiland, Piotr, Bogunia-Kubik, Katarzyna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5535923/
https://www.ncbi.nlm.nih.gov/pubmed/28677621
http://dx.doi.org/10.3390/ijms18071432
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author Gębura, Katarzyna
Świerkot, Jerzy
Wysoczańska, Barbara
Korman, Lucyna
Nowak, Beata
Wiland, Piotr
Bogunia-Kubik, Katarzyna
author_facet Gębura, Katarzyna
Świerkot, Jerzy
Wysoczańska, Barbara
Korman, Lucyna
Nowak, Beata
Wiland, Piotr
Bogunia-Kubik, Katarzyna
author_sort Gębura, Katarzyna
collection PubMed
description Genes involved in regulation of the nuclear factor-κB (NF-κB)—pathway are suggested to play a role in pathogenesis of rheumatoid arthritis (RA). In the present study, genetic polymorphisms of TLR2, TLR4, TLR9 and NF-κB1 genes were investigated to assess their associations with RA susceptibility, progression and response to anti-TNF-α therapy. A group of 110 RA patients and 126 healthy individuals were genotyped for TLR2 (rs111200466), TLR4 (rs4986790, rs4986791), TLR9 (rs5743836, rs187084) and NF-κB1 (rs28362491) alleles. The presence of the TLR9 −1486 T variant (p < 0.0001) and its homozygosity (p < 0.0001) were found to be associated with disease susceptibility. The TLR9 −1237 C allele was associated with predisposition to RA in females only (p = 0.005). Moreover, the TLR4 rs4986791 G (rs4986790 T) alleles were more frequently detected among patients with the stage IV disease (p = 0.045), and were associated with more effective response to anti-TNF-α therapy (p = 0.012). More efficient response to anti-TNF-α treatment was also observed in patients with del within the NF-κB1 gene (p = 0.047), while for the TLR9 −1486 T homozygotes, the treatment was ineffective (p = 0.018). TLR polymorphisms affect disease susceptibility and response to therapy with TNF-α inhibitors in RA patients of Caucasian origin.
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spelling pubmed-55359232017-08-04 Polymorphisms within Genes Involved in Regulation of the NF-κB Pathway in Patients with Rheumatoid Arthritis Gębura, Katarzyna Świerkot, Jerzy Wysoczańska, Barbara Korman, Lucyna Nowak, Beata Wiland, Piotr Bogunia-Kubik, Katarzyna Int J Mol Sci Article Genes involved in regulation of the nuclear factor-κB (NF-κB)—pathway are suggested to play a role in pathogenesis of rheumatoid arthritis (RA). In the present study, genetic polymorphisms of TLR2, TLR4, TLR9 and NF-κB1 genes were investigated to assess their associations with RA susceptibility, progression and response to anti-TNF-α therapy. A group of 110 RA patients and 126 healthy individuals were genotyped for TLR2 (rs111200466), TLR4 (rs4986790, rs4986791), TLR9 (rs5743836, rs187084) and NF-κB1 (rs28362491) alleles. The presence of the TLR9 −1486 T variant (p < 0.0001) and its homozygosity (p < 0.0001) were found to be associated with disease susceptibility. The TLR9 −1237 C allele was associated with predisposition to RA in females only (p = 0.005). Moreover, the TLR4 rs4986791 G (rs4986790 T) alleles were more frequently detected among patients with the stage IV disease (p = 0.045), and were associated with more effective response to anti-TNF-α therapy (p = 0.012). More efficient response to anti-TNF-α treatment was also observed in patients with del within the NF-κB1 gene (p = 0.047), while for the TLR9 −1486 T homozygotes, the treatment was ineffective (p = 0.018). TLR polymorphisms affect disease susceptibility and response to therapy with TNF-α inhibitors in RA patients of Caucasian origin. MDPI 2017-07-04 /pmc/articles/PMC5535923/ /pubmed/28677621 http://dx.doi.org/10.3390/ijms18071432 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gębura, Katarzyna
Świerkot, Jerzy
Wysoczańska, Barbara
Korman, Lucyna
Nowak, Beata
Wiland, Piotr
Bogunia-Kubik, Katarzyna
Polymorphisms within Genes Involved in Regulation of the NF-κB Pathway in Patients with Rheumatoid Arthritis
title Polymorphisms within Genes Involved in Regulation of the NF-κB Pathway in Patients with Rheumatoid Arthritis
title_full Polymorphisms within Genes Involved in Regulation of the NF-κB Pathway in Patients with Rheumatoid Arthritis
title_fullStr Polymorphisms within Genes Involved in Regulation of the NF-κB Pathway in Patients with Rheumatoid Arthritis
title_full_unstemmed Polymorphisms within Genes Involved in Regulation of the NF-κB Pathway in Patients with Rheumatoid Arthritis
title_short Polymorphisms within Genes Involved in Regulation of the NF-κB Pathway in Patients with Rheumatoid Arthritis
title_sort polymorphisms within genes involved in regulation of the nf-κb pathway in patients with rheumatoid arthritis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5535923/
https://www.ncbi.nlm.nih.gov/pubmed/28677621
http://dx.doi.org/10.3390/ijms18071432
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