The rs5743836 polymorphism in TLR9 confers a population-based increased risk of non-Hodgkin lymphoma
Autor(a) principal: | |
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Data de Publicação: | 2012 |
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/10400.23/565 |
Resumo: | Non-Hodgkin lymphoma (NHL) has been associated with immunological defects, chronic inflammatory and autoimmune conditions. Given the link between immune dysfunction and NHL, genetic variants in toll-like receptors (TLRs) have been regarded as potential predictive factors of susceptibility to NHL. Adequate anti-tumoral responses are known to depend on TLR9 function, such that the use of its synthetic ligand is being targeted as a therapeutic strategy. We investigated the association between the functional rs5743836 polymorphism in the TLR9 promoter and risk for B-cell NHL and its major subtypes in three independent case-control association studies from Portugal (1160 controls, 797 patients), Italy (468 controls, 494 patients) and the US (972 controls, 868 patients). We found that the rs5743836 polymorphism was significantly overtransmitted in both Portuguese (odds ratio (OR), 1.85; P=7.3E-9) and Italian (OR, 1.84; P=6.0E-5) and not in the US cohort of NHL patients. Moreover, the increased transcriptional activity of TLR9 in mononuclear cells from patients harboring rs5743836 further supports a functional effect of this polymorphism on NHL susceptibility in a population-dependent manner. |
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The rs5743836 polymorphism in TLR9 confers a population-based increased risk of non-Hodgkin lymphomaLinfoma Não-HodgkinPolimorfismo GenéticoReceptor "Toll-Like" 9Non-Hodgkin lymphoma (NHL) has been associated with immunological defects, chronic inflammatory and autoimmune conditions. Given the link between immune dysfunction and NHL, genetic variants in toll-like receptors (TLRs) have been regarded as potential predictive factors of susceptibility to NHL. Adequate anti-tumoral responses are known to depend on TLR9 function, such that the use of its synthetic ligand is being targeted as a therapeutic strategy. We investigated the association between the functional rs5743836 polymorphism in the TLR9 promoter and risk for B-cell NHL and its major subtypes in three independent case-control association studies from Portugal (1160 controls, 797 patients), Italy (468 controls, 494 patients) and the US (972 controls, 868 patients). We found that the rs5743836 polymorphism was significantly overtransmitted in both Portuguese (odds ratio (OR), 1.85; P=7.3E-9) and Italian (OR, 1.84; P=6.0E-5) and not in the US cohort of NHL patients. Moreover, the increased transcriptional activity of TLR9 in mononuclear cells from patients harboring rs5743836 further supports a functional effect of this polymorphism on NHL susceptibility in a population-dependent manner.Nature Publishing GroupRepositório Científico do Hospital de BragaCarvalho, ACunha, CAlmeida, AJOsório, NSSaraiva, MTeixeira-Coelho, MPedreiro, STorrado, EDomingues, NGomes-Alves, AGMarques, ASilva MGLacerda, JFGomes, MPinto, ACTorres, FRendeiro, PTavares, PDi Ianni, MHeutink, PBracci, PMConde, LLudovico, PPedrosa, JMaciel, PPitzurra, LAversa, FMarques, HPaiva, ASkibola, CFRomani, LCastro, AGRodrigues, F2013-12-13T16:15:46Z2012-01-01T00:00:00Z2012-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.23/565engGenes Immun. 2012;13(2):197-201.info: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:RCAAP2022-09-21T09:02:15Zoai:repositorio.hospitaldebraga.pt:10400.23/565Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T15:55:12.961563Repositório 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 |
The rs5743836 polymorphism in TLR9 confers a population-based increased risk of non-Hodgkin lymphoma |
title |
The rs5743836 polymorphism in TLR9 confers a population-based increased risk of non-Hodgkin lymphoma |
spellingShingle |
The rs5743836 polymorphism in TLR9 confers a population-based increased risk of non-Hodgkin lymphoma Carvalho, A Linfoma Não-Hodgkin Polimorfismo Genético Receptor "Toll-Like" 9 |
title_short |
The rs5743836 polymorphism in TLR9 confers a population-based increased risk of non-Hodgkin lymphoma |
title_full |
The rs5743836 polymorphism in TLR9 confers a population-based increased risk of non-Hodgkin lymphoma |
title_fullStr |
The rs5743836 polymorphism in TLR9 confers a population-based increased risk of non-Hodgkin lymphoma |
title_full_unstemmed |
The rs5743836 polymorphism in TLR9 confers a population-based increased risk of non-Hodgkin lymphoma |
title_sort |
The rs5743836 polymorphism in TLR9 confers a population-based increased risk of non-Hodgkin lymphoma |
author |
Carvalho, A |
author_facet |
Carvalho, A Cunha, C Almeida, AJ Osório, NS Saraiva, M Teixeira-Coelho, M Pedreiro, S Torrado, E Domingues, N Gomes-Alves, AG Marques, A Silva MG Lacerda, JF Gomes, M Pinto, AC Torres, F Rendeiro, P Tavares, P Di Ianni, M Heutink, P Bracci, PM Conde, L Ludovico, P Pedrosa, J Maciel, P Pitzurra, L Aversa, F Marques, H Paiva, A Skibola, CF Romani, L Castro, AG Rodrigues, F |
author_role |
author |
author2 |
Cunha, C Almeida, AJ Osório, NS Saraiva, M Teixeira-Coelho, M Pedreiro, S Torrado, E Domingues, N Gomes-Alves, AG Marques, A Silva MG Lacerda, JF Gomes, M Pinto, AC Torres, F Rendeiro, P Tavares, P Di Ianni, M Heutink, P Bracci, PM Conde, L Ludovico, P Pedrosa, J Maciel, P Pitzurra, L Aversa, F Marques, H Paiva, A Skibola, CF Romani, L Castro, AG Rodrigues, F |
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 author author author |
dc.contributor.none.fl_str_mv |
Repositório Científico do Hospital de Braga |
dc.contributor.author.fl_str_mv |
Carvalho, A Cunha, C Almeida, AJ Osório, NS Saraiva, M Teixeira-Coelho, M Pedreiro, S Torrado, E Domingues, N Gomes-Alves, AG Marques, A Silva MG Lacerda, JF Gomes, M Pinto, AC Torres, F Rendeiro, P Tavares, P Di Ianni, M Heutink, P Bracci, PM Conde, L Ludovico, P Pedrosa, J Maciel, P Pitzurra, L Aversa, F Marques, H Paiva, A Skibola, CF Romani, L Castro, AG Rodrigues, F |
dc.subject.por.fl_str_mv |
Linfoma Não-Hodgkin Polimorfismo Genético Receptor "Toll-Like" 9 |
topic |
Linfoma Não-Hodgkin Polimorfismo Genético Receptor "Toll-Like" 9 |
description |
Non-Hodgkin lymphoma (NHL) has been associated with immunological defects, chronic inflammatory and autoimmune conditions. Given the link between immune dysfunction and NHL, genetic variants in toll-like receptors (TLRs) have been regarded as potential predictive factors of susceptibility to NHL. Adequate anti-tumoral responses are known to depend on TLR9 function, such that the use of its synthetic ligand is being targeted as a therapeutic strategy. We investigated the association between the functional rs5743836 polymorphism in the TLR9 promoter and risk for B-cell NHL and its major subtypes in three independent case-control association studies from Portugal (1160 controls, 797 patients), Italy (468 controls, 494 patients) and the US (972 controls, 868 patients). We found that the rs5743836 polymorphism was significantly overtransmitted in both Portuguese (odds ratio (OR), 1.85; P=7.3E-9) and Italian (OR, 1.84; P=6.0E-5) and not in the US cohort of NHL patients. Moreover, the increased transcriptional activity of TLR9 in mononuclear cells from patients harboring rs5743836 further supports a functional effect of this polymorphism on NHL susceptibility in a population-dependent manner. |
publishDate |
2012 |
dc.date.none.fl_str_mv |
2012-01-01T00:00:00Z 2012-01-01T00:00:00Z 2013-12-13T16:15:46Z |
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/10400.23/565 |
url |
http://hdl.handle.net/10400.23/565 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Genes Immun. 2012;13(2):197-201. |
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 |
Nature Publishing Group |
publisher.none.fl_str_mv |
Nature Publishing Group |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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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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1799130419477610496 |