Association of rs1285933 single nucleotide polymorphism in CLEC5A gene with dengue severity and its functional effects

Detalhes bibliográficos
Autor(a) principal: Carvalho, Caroline Xavier
Data de Publicação: 2017
Outros Autores: 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
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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spelling 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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dc.publisher.none.fl_str_mv Elsevier
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