Genetic polymorphisms of the IL6 and NOD2 genes are risk factors for inflammatory reactions in leprosy

Detalhes bibliográficos
Autor(a) principal: Marques, Carolinne Sales
Data de Publicação: 2017
Outros Autores: Cardoso, Cynthia Chester, Alvarado-Arnez, Lucia Elena, Illaramendi, Ximena, Sales, Anna Maria, Hacker, Mariana de Andréa, Barbosa, Mayara Garcia de Mattos, Nery, José Augusto da Costa, Pinheiro, Roberta Olmo, Sarno, Euzenir Nunes, Pacheco, Antonio Guilherme, 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/24812
Resumo: Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ. Brasil.
id CRUZ_baf08506d59975484bc8de9e54f02585
oai_identifier_str oai:www.arca.fiocruz.br:icict/24812
network_acronym_str CRUZ
network_name_str Repositório Institucional da FIOCRUZ (ARCA)
repository_id_str 2135
spelling Marques, Carolinne SalesCardoso, Cynthia ChesterAlvarado-Arnez, Lucia ElenaIllaramendi, XimenaSales, Anna MariaHacker, Mariana de AndréaBarbosa, Mayara Garcia de MattosNery, José Augusto da CostaPinheiro, Roberta OlmoSarno, Euzenir NunesPacheco, Antonio GuilhermeMoraes, Milton Ozório2018-02-15T10:27:23Z2018-02-15T10:27:23Z2017MARQUES, Carolinne Sales et al. Genetic polymorphisms of the IL6 and NOD2 genes are risk factors for inflammatory reactions in leprosy. PLoS Neglected Tropical Diseases, v. 11, n. 7, p. 1-16, e0005754, July 2017.1935-2727https://www.arca.fiocruz.br/handle/icict/2481210.1371/journal.pntd.00057541935-2735engPublic Library of ScienceHanseníasePolimorfismo GenéticoFatores de riscoReações inflamatóriasProteína Adaptadora de Sinalização NOD2Genetic polymorphismsLeprosyRisk factorsIL6 and NOD2 genesInflammatory reactionsGenetic polymorphisms of the IL6 and NOD2 genes are risk factors for inflammatory reactions in leprosyinfo: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 Hanseníase. 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 Hanseníase. 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 Hanseníase. 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 Hanseníase. 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 Hanseníase. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Presidência. Programa de Computação Científica. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ. Brasil.The pathways that trigger exacerbated immune reactions in leprosy could be determined by genetic variations. Here, in a prospective approach, both genetic and non-genetic variables influencing the amount of time before the development of reactional episodes were studied using Kaplan-Meier survival curves, and the genetic effect was estimated by the Cox proportional-hazards regression model. In a sample including 447 leprosy patients, we confirmed that gender (male), and high bacillary clinical forms are risk factors for leprosy reactions. From the 15 single nucleotide polymorphisms (SNPs) at the 8 candidate genes genotyped (TNF/LTA, IFNG, IL10, TLR1, NOD2, SOD2, and IL6) we observed statistically different survival curves for rs751271 at the NOD2 and rs2069845 at the IL6 genes (log-rank p-values = 0.002 and 0.023, respectively), suggesting an influence on the amount of time before developing leprosy reactions. Cox models showed associations between the SNPs rs751271 at NOD2 and rs2069845 at IL6 with leprosy reactions (HRGT = 0.45, p = 0.002; HRAG = 1.88, p = 0.0008, respectively). Finally, IL-6 and IFN-γ levels were confirmed as high, while IL-10 titers were low in the sera of reactional patients. Rs751271-GT genotype-bearing individuals correlated (p = 0.05) with lower levels of IL-6 in sera samples, corroborating the genetic results. Although the experimental size may be considered a limitation of the study, the findings confirm the association of classical variables such as sex and clinical forms with leprosy, demonstrating the consistency of the results. From the results, we conclude that SNPs at the NOD2 and IL6 genes are associated with leprosy reactions as an outcome. NOD2 also has a clear functional pro-inflammatory link that is coherent with the exacerbated responses observed in these patients.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/24812/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALcarolline_marques_etal_IOC-2017.pdfcarolline_marques_etal_IOC-2017.pdfapplication/pdf2696534https://www.arca.fiocruz.br/bitstream/icict/24812/2/carolline_marques_etal_IOC-2017.pdf8696e9a058cb91e2df44920eb239771aMD52TEXTcarolline_marques_etal_IOC-2017.pdf.txtcarolline_marques_etal_IOC-2017.pdf.txtExtracted texttext/plain52745https://www.arca.fiocruz.br/bitstream/icict/24812/3/carolline_marques_etal_IOC-2017.pdf.txte3f6ecda9bb5596f02bd5804584db677MD53icict/248122023-07-13 22:13:06.293oai:www.arca.fiocruz.br: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ório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352023-07-14T01:13:06Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false
dc.title.pt_BR.fl_str_mv Genetic polymorphisms of the IL6 and NOD2 genes are risk factors for inflammatory reactions in leprosy
title Genetic polymorphisms of the IL6 and NOD2 genes are risk factors for inflammatory reactions in leprosy
spellingShingle Genetic polymorphisms of the IL6 and NOD2 genes are risk factors for inflammatory reactions in leprosy
Marques, Carolinne Sales
Hanseníase
Polimorfismo Genético
Fatores de risco
Reações inflamatórias
Proteína Adaptadora de Sinalização NOD2
Genetic polymorphisms
Leprosy
Risk factors
IL6 and NOD2 genes
Inflammatory reactions
title_short Genetic polymorphisms of the IL6 and NOD2 genes are risk factors for inflammatory reactions in leprosy
title_full Genetic polymorphisms of the IL6 and NOD2 genes are risk factors for inflammatory reactions in leprosy
title_fullStr Genetic polymorphisms of the IL6 and NOD2 genes are risk factors for inflammatory reactions in leprosy
title_full_unstemmed Genetic polymorphisms of the IL6 and NOD2 genes are risk factors for inflammatory reactions in leprosy
title_sort Genetic polymorphisms of the IL6 and NOD2 genes are risk factors for inflammatory reactions in leprosy
author Marques, Carolinne Sales
author_facet Marques, Carolinne Sales
Cardoso, Cynthia Chester
Alvarado-Arnez, Lucia Elena
Illaramendi, Ximena
Sales, Anna Maria
Hacker, Mariana de Andréa
Barbosa, Mayara Garcia de Mattos
Nery, José Augusto da Costa
Pinheiro, Roberta Olmo
Sarno, Euzenir Nunes
Pacheco, Antonio Guilherme
Moraes, Milton Ozório
author_role author
author2 Cardoso, Cynthia Chester
Alvarado-Arnez, Lucia Elena
Illaramendi, Ximena
Sales, Anna Maria
Hacker, Mariana de Andréa
Barbosa, Mayara Garcia de Mattos
Nery, José Augusto da Costa
Pinheiro, Roberta Olmo
Sarno, Euzenir Nunes
Pacheco, Antonio Guilherme
Moraes, Milton Ozório
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Marques, Carolinne Sales
Cardoso, Cynthia Chester
Alvarado-Arnez, Lucia Elena
Illaramendi, Ximena
Sales, Anna Maria
Hacker, Mariana de Andréa
Barbosa, Mayara Garcia de Mattos
Nery, José Augusto da Costa
Pinheiro, Roberta Olmo
Sarno, Euzenir Nunes
Pacheco, Antonio Guilherme
Moraes, Milton Ozório
dc.subject.other.pt_BR.fl_str_mv Hanseníase
Polimorfismo Genético
Fatores de risco
Reações inflamatórias
Proteína Adaptadora de Sinalização NOD2
topic Hanseníase
Polimorfismo Genético
Fatores de risco
Reações inflamatórias
Proteína Adaptadora de Sinalização NOD2
Genetic polymorphisms
Leprosy
Risk factors
IL6 and NOD2 genes
Inflammatory reactions
dc.subject.en.pt_BR.fl_str_mv Genetic polymorphisms
Leprosy
Risk factors
IL6 and NOD2 genes
Inflammatory reactions
description Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ. Brasil.
publishDate 2017
dc.date.issued.fl_str_mv 2017
dc.date.accessioned.fl_str_mv 2018-02-15T10:27:23Z
dc.date.available.fl_str_mv 2018-02-15T10:27:23Z
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 MARQUES, Carolinne Sales et al. Genetic polymorphisms of the IL6 and NOD2 genes are risk factors for inflammatory reactions in leprosy. PLoS Neglected Tropical Diseases, v. 11, n. 7, p. 1-16, e0005754, July 2017.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/24812
dc.identifier.issn.pt_BR.fl_str_mv 1935-2727
dc.identifier.doi.none.fl_str_mv 10.1371/journal.pntd.0005754
dc.identifier.eissn.none.fl_str_mv 1935-2735
identifier_str_mv MARQUES, Carolinne Sales et al. Genetic polymorphisms of the IL6 and NOD2 genes are risk factors for inflammatory reactions in leprosy. PLoS Neglected Tropical Diseases, v. 11, n. 7, p. 1-16, e0005754, July 2017.
1935-2727
10.1371/journal.pntd.0005754
1935-2735
url https://www.arca.fiocruz.br/handle/icict/24812
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
bitstream.url.fl_str_mv https://www.arca.fiocruz.br/bitstream/icict/24812/1/license.txt
https://www.arca.fiocruz.br/bitstream/icict/24812/2/carolline_marques_etal_IOC-2017.pdf
https://www.arca.fiocruz.br/bitstream/icict/24812/3/carolline_marques_etal_IOC-2017.pdf.txt
bitstream.checksum.fl_str_mv 5a560609d32a3863062d77ff32785d58
8696e9a058cb91e2df44920eb239771a
e3f6ecda9bb5596f02bd5804584db677
bitstream.checksumAlgorithm.fl_str_mv MD5
MD5
MD5
repository.name.fl_str_mv Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)
repository.mail.fl_str_mv repositorio.arca@fiocruz.br
_version_ 1813008921909002240

Registros relacionados