Association of rs1285933 single nucleotide polymorphism in CLEC5A gene with dengue severity and its functional effects
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
Texto Completo: | https://www.arca.fiocruz.br/handle/icict/22847 |
Resumo: | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ. Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunologia Viral. Rio de Janeiro, RJ, Brasil. |
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Carvalho, Caroline XavierCezar, Renata Duarte da SilvaFreire, Naishe MatosVasconcelos, Carla Maria Mola deSolorzano, Victor Edgar FiestasPinto, Thiago Gomes de ToledoFialho, Luciana GomesCarmo, Rodrigo Feliciano doVasconcelos, Luydson Richardson SilvaCordeiro, Marli TenórioBaptista, PauloAzeredo, Elzinandes Leal deCunha, Rivaldo Venâncio daSouza, Luiz José dePacheco, Antonio GuilhermeKubelka, Claire FernandesMoura, Patrícia Muniz Mendes Freire deMoraes, Milton Ozório2017-10-17T15:40:47Z2017-10-17T15:40:47Z2017CARVALHO, Caroline Xavier et al. Association of rs1285933 single nucleotide polymorphism in CLEC5A gene with dengue severity and its functional effects. Human Immunology, p. 1-8, 2017.0198-8859https://www.arca.fiocruz.br/handle/icict/2284710.1016/j.humimm.2017.07.013engElsevierDenguePolimorfismoFator de Necrose TumoralDengueCLEC5APolymorphismsSevere dengueSNPsTNFAssociation of rs1285933 single nucleotide polymorphism in CLEC5A gene with dengue severity and its functional effectsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ. Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunologia Viral. Rio de Janeiro, RJ, Brasil.Universidade de Pernambuco. Instituto de Ciências Biológicas. Recife, PE, Brasil.Universidade de Pernambuco. Faculdade de Ciências Médicas. Recife, PE, Brasil.Universidade de Pernambuco. Instituto de Ciências Biológicas. Recife, PE, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunologia Viral. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunologia Viral. Rio de Janeiro, RJ, Brasil.Universidade Federal do Vale do São Francisco. Colegiado de Ciências Farmacêuticas. Petrolina, PE, Brasil.Universidade de Pernambuco. Faculdade de Ciências Médicas. Recife, PE, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Parasitologia. Laboratório de Doenças Transmissíveis. Ri de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Aggeu Magalhães. LAVITE. Recife, PE, Brasil.Universidade de Pernambuco. Faculdade de Ciências Médicas. Recife, PE, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunologia Viral. Rio de Janeiro, RJ, Brasil.Universidade Federal do Mato Grosso do Su. Faculdade de Medicina. Departamento de Genética Médica. Campo Grande, MS, Brasil.Centro de Referência em Dengue e Faculdade de Medicina. Campos de Goytacazes, RJ, Brasil.Fundação Oswaldo Cruz. Presidência. Programa de Computação Científica. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunologia Viral. Rio de Janeiro, RJ, Brasil.Universidade de Pernambuco. Instituto de Ciências Biológicas. Recife, PE, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Parasitologia. Laboratório de Doenças Transmissíveis. Ri de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ. Brasil.Outbreaks of the Zika, dengue, and chikungunya viruses, especially in the Americas, pose a global threat due to their rapid spread and difficulty controlling the vector. Extreme phenotypes are often observed, from asymptomatic to severe clinical manifestations, which are well-studied in dengue. Host variations are also important contributors to disease outcomes, and many case-control studies have associated single nucleotide polymorphisms (SNPs) with severe dengue. Here, we found that the TC genotype and T-carriers for SNP rs1285933 in the C-type lectin superfamily member 5 (CLEC5A) gene was associated with severe dengue in a Northern Brazilian population (OR=2.75 and p-value=0.01, OR=2.11 and p-value=0.04, respectively). We also tested the functional effect of the CLEC5A protein and found that it is upregulated on the surface of human monocytes after in vitro dengue infection. CLEC5A was correlated with viral load inside the monocytes (Spearman r=0.55, p=0.008) and TNF production in culture supernatants (Spearman r=0.72, p=0.03). Analysis of mRNA in blood samples from DENV4-infected patients exhibiting mild symptoms showed that CLEC5A mRNA expression is correlated with TNF (r=0.67, p=0.0001) and other immune mediators. Monocytes from rs1285933 TT/TC individuals showed lower CLEC5A expression compared to CC genotypes. However, in these cells, CLEC5A was not correlated with TNF production. In summary, we confirmed that CLEC5A is genetically associated with dengue severity outcome, playing a central role during the immune response triggered by a dengue viral infection, and rs1285933 is a relevant SNP that is able to regulate signaling pathways after interactions between the dengue virus and CLEC5A receptors.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/22847/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALcaroline_carvalho_etal_IOC_2017.pdfcaroline_carvalho_etal_IOC_2017.pdfapplication/pdf1170716https://www.arca.fiocruz.br/bitstream/icict/22847/2/caroline_carvalho_etal_IOC_2017.pdf1bbcc0ec40b48fb68c5932c566cca346MD52TEXTcaroline_carvalho_etal_IOC_2017.pdf.txtcaroline_carvalho_etal_IOC_2017.pdf.txtExtracted 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dc.title.pt_BR.fl_str_mv |
Association of rs1285933 single nucleotide polymorphism in CLEC5A gene with dengue severity and its functional effects |
title |
Association of rs1285933 single nucleotide polymorphism in CLEC5A gene with dengue severity and its functional effects |
spellingShingle |
Association of rs1285933 single nucleotide polymorphism in CLEC5A gene with dengue severity and its functional effects Carvalho, Caroline Xavier Dengue Polimorfismo Fator de Necrose Tumoral Dengue CLEC5A Polymorphisms Severe dengue SNPs TNF |
title_short |
Association of rs1285933 single nucleotide polymorphism in CLEC5A gene with dengue severity and its functional effects |
title_full |
Association of rs1285933 single nucleotide polymorphism in CLEC5A gene with dengue severity and its functional effects |
title_fullStr |
Association of rs1285933 single nucleotide polymorphism in CLEC5A gene with dengue severity and its functional effects |
title_full_unstemmed |
Association of rs1285933 single nucleotide polymorphism in CLEC5A gene with dengue severity and its functional effects |
title_sort |
Association of rs1285933 single nucleotide polymorphism in CLEC5A gene with dengue severity and its functional effects |
author |
Carvalho, Caroline Xavier |
author_facet |
Carvalho, Caroline Xavier Cezar, Renata Duarte da Silva Freire, Naishe Matos Vasconcelos, Carla Maria Mola de Solorzano, Victor Edgar Fiestas Pinto, Thiago Gomes de Toledo Fialho, Luciana Gomes Carmo, Rodrigo Feliciano do Vasconcelos, Luydson Richardson Silva Cordeiro, Marli Tenório Baptista, Paulo Azeredo, Elzinandes Leal de Cunha, Rivaldo Venâncio da Souza, Luiz José de Pacheco, Antonio Guilherme Kubelka, Claire Fernandes Moura, Patrícia Muniz Mendes Freire de Moraes, Milton Ozório |
author_role |
author |
author2 |
Cezar, Renata Duarte da Silva Freire, Naishe Matos Vasconcelos, Carla Maria Mola de Solorzano, Victor Edgar Fiestas Pinto, Thiago Gomes de Toledo Fialho, Luciana Gomes Carmo, Rodrigo Feliciano do Vasconcelos, Luydson Richardson Silva Cordeiro, Marli Tenório Baptista, Paulo Azeredo, Elzinandes Leal de Cunha, Rivaldo Venâncio da Souza, Luiz José de Pacheco, Antonio Guilherme Kubelka, Claire Fernandes Moura, Patrícia Muniz Mendes Freire de Moraes, Milton Ozório |
author2_role |
author author author author author author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Carvalho, Caroline Xavier Cezar, Renata Duarte da Silva Freire, Naishe Matos Vasconcelos, Carla Maria Mola de Solorzano, Victor Edgar Fiestas Pinto, Thiago Gomes de Toledo Fialho, Luciana Gomes Carmo, Rodrigo Feliciano do Vasconcelos, Luydson Richardson Silva Cordeiro, Marli Tenório Baptista, Paulo Azeredo, Elzinandes Leal de Cunha, Rivaldo Venâncio da Souza, Luiz José de Pacheco, Antonio Guilherme Kubelka, Claire Fernandes Moura, Patrícia Muniz Mendes Freire de Moraes, Milton Ozório |
dc.subject.other.pt_BR.fl_str_mv |
Dengue Polimorfismo Fator de Necrose Tumoral |
topic |
Dengue Polimorfismo Fator de Necrose Tumoral Dengue CLEC5A Polymorphisms Severe dengue SNPs TNF |
dc.subject.en.pt_BR.fl_str_mv |
Dengue CLEC5A Polymorphisms Severe dengue SNPs TNF |
description |
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ. Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunologia Viral. Rio de Janeiro, RJ, Brasil. |
publishDate |
2017 |
dc.date.accessioned.fl_str_mv |
2017-10-17T15:40:47Z |
dc.date.available.fl_str_mv |
2017-10-17T15:40:47Z |
dc.date.issued.fl_str_mv |
2017 |
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.citation.fl_str_mv |
CARVALHO, Caroline Xavier et al. Association of rs1285933 single nucleotide polymorphism in CLEC5A gene with dengue severity and its functional effects. Human Immunology, p. 1-8, 2017. |
dc.identifier.uri.fl_str_mv |
https://www.arca.fiocruz.br/handle/icict/22847 |
dc.identifier.issn.pt_BR.fl_str_mv |
0198-8859 |
dc.identifier.doi.none.fl_str_mv |
10.1016/j.humimm.2017.07.013 |
identifier_str_mv |
CARVALHO, Caroline Xavier et al. Association of rs1285933 single nucleotide polymorphism in CLEC5A gene with dengue severity and its functional effects. Human Immunology, p. 1-8, 2017. 0198-8859 10.1016/j.humimm.2017.07.013 |
url |
https://www.arca.fiocruz.br/handle/icict/22847 |
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eng |
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eng |
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info:eu-repo/semantics/openAccess |
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openAccess |
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Elsevier |
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Elsevier |
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