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Genetic polymorphisms associated with the inflammatory response in bacterial meningitis

BACKGROUND: Bacterial meningitis (BM) is an infectious disease that results in high mortality and morbidity. Despite efficacious antibiotic therapy, neurological sequelae are often observed in patients after disease. Currently, the main challenge in BM treatment is to develop adjuvant therapies that...

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Autores principales: Fontes, Fabrícia Lima, de Araújo, Luíza Ferreira, Coutinho, Leonam Gomes, Leib, Stephen L., Agnez-Lima, Lucymara Fassarella
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4593216/
https://www.ncbi.nlm.nih.gov/pubmed/26316174
http://dx.doi.org/10.1186/s12881-015-0218-6
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author Fontes, Fabrícia Lima
de Araújo, Luíza Ferreira
Coutinho, Leonam Gomes
Leib, Stephen L.
Agnez-Lima, Lucymara Fassarella
author_facet Fontes, Fabrícia Lima
de Araújo, Luíza Ferreira
Coutinho, Leonam Gomes
Leib, Stephen L.
Agnez-Lima, Lucymara Fassarella
author_sort Fontes, Fabrícia Lima
collection PubMed
description BACKGROUND: Bacterial meningitis (BM) is an infectious disease that results in high mortality and morbidity. Despite efficacious antibiotic therapy, neurological sequelae are often observed in patients after disease. Currently, the main challenge in BM treatment is to develop adjuvant therapies that reduce the occurrence of sequelae. In recent papers published by our group, we described the associations between the single nucleotide polymorphisms (SNPs) AADAT +401C > T, APEX1 Asn148Glu, OGG1 Ser326Cys and PARP1 Val762Ala and BM. In this study, we analyzed the associations between the SNPs TNF -308G > A, TNF -857C > T, IL-8 -251A > T and BM and investigated gene-gene interactions, including the SNPs that we published previously. METHODS: The study was conducted with 54 BM patients and 110 healthy volunteers (as the control group). The genotypes were investigated via primer-introduced restriction analysis-polymerase chain reaction (PIRA-PCR) or polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) analysis. Allelic and genotypic frequencies were also associated with cytokine and chemokine levels, as measured with the x-MAP method, and cell counts. We analyzed gene-gene interactions among SNPs using the generalized multifactor dimensionality reduction (GMDR) method. RESULTS: We did not find significant association between the SNPs TNF -857C > T and IL-8 -251A > T and the disease. However, a higher frequency of the variant allele TNF -308A was observed in the control group, associated with changes in cytokine levels compared to individuals with wild type genotypes, suggesting a possible protective role. In addition, combined inter-gene interaction analysis indicated a significant association between certain genotypes and BM, mainly involving the alleles APEX1 148Glu, IL8 -251 T and AADAT +401 T. These genotypic combinations were shown to affect cyto/chemokine levels and cell counts in CSF samples from BM patients. CONCLUSIONS: In conclusion, this study revealed a significant association between genetic variability and altered inflammatory responses, involving important pathways that are activated during BM. This knowledge may be useful for a better understanding of BM pathogenesis and the development of new therapeutic approaches. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12881-015-0218-6) contains supplementary material, which is available to authorized users.
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spelling pubmed-45932162015-10-06 Genetic polymorphisms associated with the inflammatory response in bacterial meningitis Fontes, Fabrícia Lima de Araújo, Luíza Ferreira Coutinho, Leonam Gomes Leib, Stephen L. Agnez-Lima, Lucymara Fassarella BMC Med Genet Research Article BACKGROUND: Bacterial meningitis (BM) is an infectious disease that results in high mortality and morbidity. Despite efficacious antibiotic therapy, neurological sequelae are often observed in patients after disease. Currently, the main challenge in BM treatment is to develop adjuvant therapies that reduce the occurrence of sequelae. In recent papers published by our group, we described the associations between the single nucleotide polymorphisms (SNPs) AADAT +401C > T, APEX1 Asn148Glu, OGG1 Ser326Cys and PARP1 Val762Ala and BM. In this study, we analyzed the associations between the SNPs TNF -308G > A, TNF -857C > T, IL-8 -251A > T and BM and investigated gene-gene interactions, including the SNPs that we published previously. METHODS: The study was conducted with 54 BM patients and 110 healthy volunteers (as the control group). The genotypes were investigated via primer-introduced restriction analysis-polymerase chain reaction (PIRA-PCR) or polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) analysis. Allelic and genotypic frequencies were also associated with cytokine and chemokine levels, as measured with the x-MAP method, and cell counts. We analyzed gene-gene interactions among SNPs using the generalized multifactor dimensionality reduction (GMDR) method. RESULTS: We did not find significant association between the SNPs TNF -857C > T and IL-8 -251A > T and the disease. However, a higher frequency of the variant allele TNF -308A was observed in the control group, associated with changes in cytokine levels compared to individuals with wild type genotypes, suggesting a possible protective role. In addition, combined inter-gene interaction analysis indicated a significant association between certain genotypes and BM, mainly involving the alleles APEX1 148Glu, IL8 -251 T and AADAT +401 T. These genotypic combinations were shown to affect cyto/chemokine levels and cell counts in CSF samples from BM patients. CONCLUSIONS: In conclusion, this study revealed a significant association between genetic variability and altered inflammatory responses, involving important pathways that are activated during BM. This knowledge may be useful for a better understanding of BM pathogenesis and the development of new therapeutic approaches. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12881-015-0218-6) contains supplementary material, which is available to authorized users. BioMed Central 2015-08-28 /pmc/articles/PMC4593216/ /pubmed/26316174 http://dx.doi.org/10.1186/s12881-015-0218-6 Text en © Fontes et al. 2015 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Fontes, Fabrícia Lima
de Araújo, Luíza Ferreira
Coutinho, Leonam Gomes
Leib, Stephen L.
Agnez-Lima, Lucymara Fassarella
Genetic polymorphisms associated with the inflammatory response in bacterial meningitis
title Genetic polymorphisms associated with the inflammatory response in bacterial meningitis
title_full Genetic polymorphisms associated with the inflammatory response in bacterial meningitis
title_fullStr Genetic polymorphisms associated with the inflammatory response in bacterial meningitis
title_full_unstemmed Genetic polymorphisms associated with the inflammatory response in bacterial meningitis
title_short Genetic polymorphisms associated with the inflammatory response in bacterial meningitis
title_sort genetic polymorphisms associated with the inflammatory response in bacterial meningitis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4593216/
https://www.ncbi.nlm.nih.gov/pubmed/26316174
http://dx.doi.org/10.1186/s12881-015-0218-6
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