Genetic polymorphisms of the IL6 and NOD2 genes are risk factors for inflammatory reactions in leprosy.
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 c...
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ftdoajarticles:oai:doaj.org/article:e00ba8e315fc4eefac5698ec35a54820 2023-05-15T15:15:28+02:00 Genetic polymorphisms of the IL6 and NOD2 genes are risk factors for inflammatory reactions in leprosy. Carolinne Sales-Marques Cynthia Chester Cardoso Lucia Elena Alvarado-Arnez Ximena Illaramendi Anna Maria Sales Mariana de Andréa Hacker Mayara Garcia de Mattos Barbosa José Augusto da Costa Nery Roberta Olmo Pinheiro Euzenir Nunes Sarno Antonio Guilherme Pacheco Milton Ozório Moraes 2017-07-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0005754 https://doaj.org/article/e00ba8e315fc4eefac5698ec35a54820 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC5531687?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0005754 https://doaj.org/article/e00ba8e315fc4eefac5698ec35a54820 PLoS Neglected Tropical Diseases, Vol 11, Iss 7, p e0005754 (2017) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2017 ftdoajarticles https://doi.org/10.1371/journal.pntd.0005754 2022-12-31T01:48:57Z 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. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Meier ENVELOPE(-45.900,-45.900,-60.633,-60.633) PLOS Neglected Tropical Diseases 11 7 e0005754 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Carolinne Sales-Marques Cynthia Chester Cardoso Lucia Elena Alvarado-Arnez Ximena Illaramendi Anna Maria Sales Mariana de Andréa Hacker Mayara Garcia de Mattos Barbosa José Augusto da Costa Nery Roberta Olmo Pinheiro Euzenir Nunes Sarno Antonio Guilherme Pacheco Milton Ozório Moraes Genetic polymorphisms of the IL6 and NOD2 genes are risk factors for inflammatory reactions in leprosy. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
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. |
format |
Article in Journal/Newspaper |
author |
Carolinne Sales-Marques Cynthia Chester Cardoso Lucia Elena Alvarado-Arnez Ximena Illaramendi Anna Maria Sales Mariana de Andréa Hacker Mayara Garcia de Mattos Barbosa José Augusto da Costa Nery Roberta Olmo Pinheiro Euzenir Nunes Sarno Antonio Guilherme Pacheco Milton Ozório Moraes |
author_facet |
Carolinne Sales-Marques Cynthia Chester Cardoso Lucia Elena Alvarado-Arnez Ximena Illaramendi Anna Maria Sales Mariana de Andréa Hacker Mayara Garcia de Mattos Barbosa José Augusto da Costa Nery Roberta Olmo Pinheiro Euzenir Nunes Sarno Antonio Guilherme Pacheco Milton Ozório Moraes |
author_sort |
Carolinne Sales-Marques |
title |
Genetic polymorphisms of the IL6 and NOD2 genes are risk factors for inflammatory reactions in leprosy. |
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. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2017 |
url |
https://doi.org/10.1371/journal.pntd.0005754 https://doaj.org/article/e00ba8e315fc4eefac5698ec35a54820 |
long_lat |
ENVELOPE(-45.900,-45.900,-60.633,-60.633) |
geographic |
Arctic Meier |
geographic_facet |
Arctic Meier |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 11, Iss 7, p e0005754 (2017) |
op_relation |
http://europepmc.org/articles/PMC5531687?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0005754 https://doaj.org/article/e00ba8e315fc4eefac5698ec35a54820 |
op_doi |
https://doi.org/10.1371/journal.pntd.0005754 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
11 |
container_issue |
7 |
container_start_page |
e0005754 |
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1766345833720053760 |