Common genetic polymorphisms within NFκB-Related genes and the risk of developing invasive aspergillosis
Autor(a) principal: | |
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Data de Publicação: | 2016 |
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/1822/51988 |
Resumo: | Invasive Aspergillosis (IA) is an opportunistic infection caused by Aspergillus, a ubiquitously present airborne pathogenic mold. A growing number of studies suggest a major host genetic component in disease susceptibility. Here, we evaluated whether 14 single-nucleotide polymorphisms within NF kappa B1, NF kappa B2, RelA, RelB, Rel, and IRF4 genes influence the risk of IA in a population of 834 high-risk patients (157 IA and 677 non IA) recruited through a collaborative effort involving the aspBlOmics consortium and four European clinical institutions. No significant overall associations between selected SNPs and the risk of IA were found in this large cohort. Although a hematopoietic stem cell transplantation (HSCT)-stratified analysis revealed that carriers of the IRF4(rs12203592T/T) genotype had a six-fold increased risk of developing the infection when compared with those carrying the C allele (ORREC = 6.24, 95%CI 1.25-31.2, P = 0.026), the association of this variant with IA risk did not reach significance at experiment-wide significant threshold. In addition, we found an association of the IRF4(AATC) and IRF4(GGTC) haplotypes (not including the IRF4(rs12203592T/T) risk allele) with a decreased risk of IA but the magnitude of the association was similar to the one observed in the single-SNP analysis, which indicated that the haplotypic effect on IA risk was likely due to the IRF4(rs12203592) SNP Finally, no evidence of significant interactions among the genetic markers tested and the risk of IA was found. These results suggest that the SNPs on the studied genes do not have a clinically relevant impact on the risk of developing IA. |
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Common genetic polymorphisms within NFκB-Related genes and the risk of developing invasive aspergillosisInvasive AspergillosisGenetic polymorphismsSusceptibilityNF kappa B-related genesInteractionInvasive Aspergillosis, genetic polymorphisms, susceptibility, NFκB-related genes, interactionCiências Médicas::Medicina BásicaScience & TechnologyInvasive Aspergillosis (IA) is an opportunistic infection caused by Aspergillus, a ubiquitously present airborne pathogenic mold. A growing number of studies suggest a major host genetic component in disease susceptibility. Here, we evaluated whether 14 single-nucleotide polymorphisms within NF kappa B1, NF kappa B2, RelA, RelB, Rel, and IRF4 genes influence the risk of IA in a population of 834 high-risk patients (157 IA and 677 non IA) recruited through a collaborative effort involving the aspBlOmics consortium and four European clinical institutions. No significant overall associations between selected SNPs and the risk of IA were found in this large cohort. Although a hematopoietic stem cell transplantation (HSCT)-stratified analysis revealed that carriers of the IRF4(rs12203592T/T) genotype had a six-fold increased risk of developing the infection when compared with those carrying the C allele (ORREC = 6.24, 95%CI 1.25-31.2, P = 0.026), the association of this variant with IA risk did not reach significance at experiment-wide significant threshold. In addition, we found an association of the IRF4(AATC) and IRF4(GGTC) haplotypes (not including the IRF4(rs12203592T/T) risk allele) with a decreased risk of IA but the magnitude of the association was similar to the one observed in the single-SNP analysis, which indicated that the haplotypic effect on IA risk was likely due to the IRF4(rs12203592) SNP Finally, no evidence of significant interactions among the genetic markers tested and the risk of IA was found. These results suggest that the SNPs on the studied genes do not have a clinically relevant impact on the risk of developing IA.- This study was supported by grants PI12/02688 from Fond de Investigaciones Sanitarias (Institute de Salud Carlos III, Madrid, Spain), the ERA-NET PathoGenoMics (03159000A; Ministerio de Ciencia e Innovation PIM2010EPA-00756, Madrid, Spain), the Collaborative Research Center / Transregio 124 FungiNet, the Austrian Science Fundation (FWF I-656-B09), the Fundacao para a Ciencia e Tecnologia (FCT), cofundcd by Programa Operacional Regional do Norte (ON.2-O Novo Norte), the Quadro de Referencia Estrategico Nacional (QREN) through the Fundo Europeu de Desenvolvimento Regional (FEDER) and the Projeto Estrategico - LA 26 - 2013-2014 (PEst-C/SAU/LA0026/2013). Agostinho Carvalho and Cristina Cunha were supported by the Fundacao para a e Tecnologia (FCT), Portugal (IF/00735/2014 and SFRH/BPD/96176/2013, respectively). The PCRAGA trial was supported by an unrestricted grant from Pfizer, which had no involvement or control over the collection, analysis, and interpretation of data; the writing of the report; or the decision to submit the paper for publication. This study was also supported by Astellas Pharma Inc. and a donation from Consuelo Gonzalez Moreno, an acute myeloid leukemia survivor.info:eu-repo/semantics/publishedVersionFrontiers MediaUniversidade do MinhoLupianez, Carmen B.Villaescusa, Maria T.Carvalho, AgostinhoSpringer, JanLackner, MichaelaSanchez-Maldonado, Jose M.Canet, Luz M.Cunha, CristinaSegura-Catena, JuanaAlcazar-Fuoli, LauraSolano, CarlosFianchi, LuanaPagano, LivioPotenza, LeonardoAguado, Jose M.Luppi, MarioCuenca-Estrella, ManuelLass-Floerl, CorneliaEinsele, HermannVazquez, LourdesRios-Tamayo, RafaelLoeffler, JurgenJurado, ManuelSainz, Juanet. al.2016-08-122016-08-12T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/51988engLupiañez, C. B., Villaescusa, M. T., Carvalho, A., Springer, J., Lackner, M., Sánchez-Maldonado, J. M., ... & Solano, C. (2016). Common genetic polymorphisms within NFκB-related genes and the risk of developing invasive aspergillosis. Frontiers in microbiology, 7, 1243.1664-302X10.3389/fmicb.2016.01243https://www.frontiersin.org/articles/10.3389/fmicb.2016.01243/fullinfo: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:RCAAP2023-07-21T12:08:01Zoai:repositorium.sdum.uminho.pt:1822/51988Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:59:08.174978Repositório 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 |
Common genetic polymorphisms within NFκB-Related genes and the risk of developing invasive aspergillosis |
title |
Common genetic polymorphisms within NFκB-Related genes and the risk of developing invasive aspergillosis |
spellingShingle |
Common genetic polymorphisms within NFκB-Related genes and the risk of developing invasive aspergillosis Lupianez, Carmen B. Invasive Aspergillosis Genetic polymorphisms Susceptibility NF kappa B-related genes Interaction Invasive Aspergillosis, genetic polymorphisms, susceptibility, NFκB-related genes, interaction Ciências Médicas::Medicina Básica Science & Technology |
title_short |
Common genetic polymorphisms within NFκB-Related genes and the risk of developing invasive aspergillosis |
title_full |
Common genetic polymorphisms within NFκB-Related genes and the risk of developing invasive aspergillosis |
title_fullStr |
Common genetic polymorphisms within NFκB-Related genes and the risk of developing invasive aspergillosis |
title_full_unstemmed |
Common genetic polymorphisms within NFκB-Related genes and the risk of developing invasive aspergillosis |
title_sort |
Common genetic polymorphisms within NFκB-Related genes and the risk of developing invasive aspergillosis |
author |
Lupianez, Carmen B. |
author_facet |
Lupianez, Carmen B. Villaescusa, Maria T. Carvalho, Agostinho Springer, Jan Lackner, Michaela Sanchez-Maldonado, Jose M. Canet, Luz M. Cunha, Cristina Segura-Catena, Juana Alcazar-Fuoli, Laura Solano, Carlos Fianchi, Luana Pagano, Livio Potenza, Leonardo Aguado, Jose M. Luppi, Mario Cuenca-Estrella, Manuel Lass-Floerl, Cornelia Einsele, Hermann Vazquez, Lourdes Rios-Tamayo, Rafael Loeffler, Jurgen Jurado, Manuel Sainz, Juan et. al. |
author_role |
author |
author2 |
Villaescusa, Maria T. Carvalho, Agostinho Springer, Jan Lackner, Michaela Sanchez-Maldonado, Jose M. Canet, Luz M. Cunha, Cristina Segura-Catena, Juana Alcazar-Fuoli, Laura Solano, Carlos Fianchi, Luana Pagano, Livio Potenza, Leonardo Aguado, Jose M. Luppi, Mario Cuenca-Estrella, Manuel Lass-Floerl, Cornelia Einsele, Hermann Vazquez, Lourdes Rios-Tamayo, Rafael Loeffler, Jurgen Jurado, Manuel Sainz, Juan et. al. |
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 |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Lupianez, Carmen B. Villaescusa, Maria T. Carvalho, Agostinho Springer, Jan Lackner, Michaela Sanchez-Maldonado, Jose M. Canet, Luz M. Cunha, Cristina Segura-Catena, Juana Alcazar-Fuoli, Laura Solano, Carlos Fianchi, Luana Pagano, Livio Potenza, Leonardo Aguado, Jose M. Luppi, Mario Cuenca-Estrella, Manuel Lass-Floerl, Cornelia Einsele, Hermann Vazquez, Lourdes Rios-Tamayo, Rafael Loeffler, Jurgen Jurado, Manuel Sainz, Juan et. al. |
dc.subject.por.fl_str_mv |
Invasive Aspergillosis Genetic polymorphisms Susceptibility NF kappa B-related genes Interaction Invasive Aspergillosis, genetic polymorphisms, susceptibility, NFκB-related genes, interaction Ciências Médicas::Medicina Básica Science & Technology |
topic |
Invasive Aspergillosis Genetic polymorphisms Susceptibility NF kappa B-related genes Interaction Invasive Aspergillosis, genetic polymorphisms, susceptibility, NFκB-related genes, interaction Ciências Médicas::Medicina Básica Science & Technology |
description |
Invasive Aspergillosis (IA) is an opportunistic infection caused by Aspergillus, a ubiquitously present airborne pathogenic mold. A growing number of studies suggest a major host genetic component in disease susceptibility. Here, we evaluated whether 14 single-nucleotide polymorphisms within NF kappa B1, NF kappa B2, RelA, RelB, Rel, and IRF4 genes influence the risk of IA in a population of 834 high-risk patients (157 IA and 677 non IA) recruited through a collaborative effort involving the aspBlOmics consortium and four European clinical institutions. No significant overall associations between selected SNPs and the risk of IA were found in this large cohort. Although a hematopoietic stem cell transplantation (HSCT)-stratified analysis revealed that carriers of the IRF4(rs12203592T/T) genotype had a six-fold increased risk of developing the infection when compared with those carrying the C allele (ORREC = 6.24, 95%CI 1.25-31.2, P = 0.026), the association of this variant with IA risk did not reach significance at experiment-wide significant threshold. In addition, we found an association of the IRF4(AATC) and IRF4(GGTC) haplotypes (not including the IRF4(rs12203592T/T) risk allele) with a decreased risk of IA but the magnitude of the association was similar to the one observed in the single-SNP analysis, which indicated that the haplotypic effect on IA risk was likely due to the IRF4(rs12203592) SNP Finally, no evidence of significant interactions among the genetic markers tested and the risk of IA was found. These results suggest that the SNPs on the studied genes do not have a clinically relevant impact on the risk of developing IA. |
publishDate |
2016 |
dc.date.none.fl_str_mv |
2016-08-12 2016-08-12T00:00:00Z |
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/1822/51988 |
url |
http://hdl.handle.net/1822/51988 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Lupiañez, C. B., Villaescusa, M. T., Carvalho, A., Springer, J., Lackner, M., Sánchez-Maldonado, J. M., ... & Solano, C. (2016). Common genetic polymorphisms within NFκB-related genes and the risk of developing invasive aspergillosis. Frontiers in microbiology, 7, 1243. 1664-302X 10.3389/fmicb.2016.01243 https://www.frontiersin.org/articles/10.3389/fmicb.2016.01243/full |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Frontiers Media |
publisher.none.fl_str_mv |
Frontiers Media |
dc.source.none.fl_str_mv |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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