NFKB2 polymorphisms associate with the risk of developing rheumatoid arthritis and response to TNF inhibitors : results from the REPAIR consortium
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10451/46631 |
Resumo: | © The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Cre-ative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not per-mitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
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NFKB2 polymorphisms associate with the risk of developing rheumatoid arthritis and response to TNF inhibitors : results from the REPAIR consortium© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Cre-ative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not per-mitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.This study sought to evaluate the association of 28 single nucleotide polymorphisms (SNPs) within NFKB and inflammasome pathway genes with the risk of rheumatoid arthritis (RA) and response to TNF inhibitors (TNFi). We conducted a case-control study in a European population of 1194 RA patients and 1328 healthy controls. The association of potentially interesting markers was validated with data from the DANBIO (695 RA patients and 978 healthy controls) and DREAM (882 RA patients) registries. The meta-analysis of our data with those from the DANBIO registry confirmed that anti-citrullinated protein antibodies (ACPA)-positive subjects carrying the NFKB2rs11574851T allele had a significantly increased risk of developing RA (PMeta_ACPA + = 0.0006) whereas no significant effect was found in ACPA-negative individuals (PMeta_ACPA- = 0.35). An ACPA-stratified haplotype analysis including both cohorts (n = 4210) confirmed that ACPA-positive subjects carrying the NFKB2TT haplotype had an increased risk of RA (OR = 1.39, P = 0.0042) whereas no effect was found in ACPA-negative subjects (OR = 1.04, P = 0.82). The meta-analysis of our data with those from the DANBIO and DREAM registries also revealed a suggestive association of the NFKB2rs1056890 SNP with larger changes in DAS28 (OR = 1.18, P = 0.007). Functional experiments showed that peripheral blood mononuclear cells from carriers of the NFKB2rs1005044C allele (in LD with the rs1056890, r2 = 1.00) showed increased production of IL10 after stimulation with LPS (P = 0.0026). These results provide first evidence of a role of the NFKB2 locus in modulating the risk of RA in an ACPA-dependent manner and suggest its implication in determining the response to TNFi. Additional studies are now warranted to further validate these findings.Springer NatureRepositório da Universidade de LisboaManuel Sánchez-Maldonado, JoseMartínez-Bueno, ManuelCanhao, Helenater Horst, RobMuñoz-Peña, SoniaMoñiz-Díez, AnaRodríguez-Ramos, AnaEscudero, AlejandroSorensen, Signe B.Hetland, Merete L.Ferrer, Miguel A.Glintborg, BenteFilipescu, IleanaPérez-Pampin, EvaConesa-Zamora, PabloGarcía, Antonioden Broeder, AlfonsDe Vita, SalvatoreHove Jacobsen, Svend ErikCollantes, EduardoQuartuccio, LucaNetea, Mihai G.Li, YangFonseca, João EuricoJurado, ManuelLópez-Nevot, Miguel ÁngelCoenen, Marieke J. H.Andersen, VibekeCáliz, RafaelSainz, Juan2021-03-03T17:37:41Z20202020-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/46631engSci Rep 10, 4316 (2020)10.1038/s41598-020-61331-52045-2322info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T16:49:03Zoai:repositorio.ul.pt:10451/46631Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:58:46.494467Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
NFKB2 polymorphisms associate with the risk of developing rheumatoid arthritis and response to TNF inhibitors : results from the REPAIR consortium |
title |
NFKB2 polymorphisms associate with the risk of developing rheumatoid arthritis and response to TNF inhibitors : results from the REPAIR consortium |
spellingShingle |
NFKB2 polymorphisms associate with the risk of developing rheumatoid arthritis and response to TNF inhibitors : results from the REPAIR consortium Manuel Sánchez-Maldonado, Jose |
title_short |
NFKB2 polymorphisms associate with the risk of developing rheumatoid arthritis and response to TNF inhibitors : results from the REPAIR consortium |
title_full |
NFKB2 polymorphisms associate with the risk of developing rheumatoid arthritis and response to TNF inhibitors : results from the REPAIR consortium |
title_fullStr |
NFKB2 polymorphisms associate with the risk of developing rheumatoid arthritis and response to TNF inhibitors : results from the REPAIR consortium |
title_full_unstemmed |
NFKB2 polymorphisms associate with the risk of developing rheumatoid arthritis and response to TNF inhibitors : results from the REPAIR consortium |
title_sort |
NFKB2 polymorphisms associate with the risk of developing rheumatoid arthritis and response to TNF inhibitors : results from the REPAIR consortium |
author |
Manuel Sánchez-Maldonado, Jose |
author_facet |
Manuel Sánchez-Maldonado, Jose Martínez-Bueno, Manuel Canhao, Helena ter Horst, Rob Muñoz-Peña, Sonia Moñiz-Díez, Ana Rodríguez-Ramos, Ana Escudero, Alejandro Sorensen, Signe B. Hetland, Merete L. Ferrer, Miguel A. Glintborg, Bente Filipescu, Ileana Pérez-Pampin, Eva Conesa-Zamora, Pablo García, Antonio den Broeder, Alfons De Vita, Salvatore Hove Jacobsen, Svend Erik Collantes, Eduardo Quartuccio, Luca Netea, Mihai G. Li, Yang Fonseca, João Eurico Jurado, Manuel López-Nevot, Miguel Ángel Coenen, Marieke J. H. Andersen, Vibeke Cáliz, Rafael Sainz, Juan |
author_role |
author |
author2 |
Martínez-Bueno, Manuel Canhao, Helena ter Horst, Rob Muñoz-Peña, Sonia Moñiz-Díez, Ana Rodríguez-Ramos, Ana Escudero, Alejandro Sorensen, Signe B. Hetland, Merete L. Ferrer, Miguel A. Glintborg, Bente Filipescu, Ileana Pérez-Pampin, Eva Conesa-Zamora, Pablo García, Antonio den Broeder, Alfons De Vita, Salvatore Hove Jacobsen, Svend Erik Collantes, Eduardo Quartuccio, Luca Netea, Mihai G. Li, Yang Fonseca, João Eurico Jurado, Manuel López-Nevot, Miguel Ángel Coenen, Marieke J. H. Andersen, Vibeke Cáliz, Rafael Sainz, Juan |
author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Repositório da Universidade de Lisboa |
dc.contributor.author.fl_str_mv |
Manuel Sánchez-Maldonado, Jose Martínez-Bueno, Manuel Canhao, Helena ter Horst, Rob Muñoz-Peña, Sonia Moñiz-Díez, Ana Rodríguez-Ramos, Ana Escudero, Alejandro Sorensen, Signe B. Hetland, Merete L. Ferrer, Miguel A. Glintborg, Bente Filipescu, Ileana Pérez-Pampin, Eva Conesa-Zamora, Pablo García, Antonio den Broeder, Alfons De Vita, Salvatore Hove Jacobsen, Svend Erik Collantes, Eduardo Quartuccio, Luca Netea, Mihai G. Li, Yang Fonseca, João Eurico Jurado, Manuel López-Nevot, Miguel Ángel Coenen, Marieke J. H. Andersen, Vibeke Cáliz, Rafael Sainz, Juan |
description |
© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Cre-ative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not per-mitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020 2020-01-01T00:00:00Z 2021-03-03T17:37:41Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10451/46631 |
url |
http://hdl.handle.net/10451/46631 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Sci Rep 10, 4316 (2020) 10.1038/s41598-020-61331-5 2045-2322 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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Springer Nature |
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Springer Nature |
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