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Gene Polymorphisms of TLR4 and TLR9 and Haemophilus influenzae Meningitis in Angolan Children

Bacterial meningitis (BM) is a severe disease caused by various bacterial pathogens. Toll-like receptors (TLRs) protect humans from invading pathogens. In this study, we determined whether single nucleotide polymorphisms (SNPs) of TLR4 and TLR9 are associated with susceptibility to and outcome of BM...

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Autores principales: Tenhu, Elina, Teräsjärvi, Johanna, Cruzeiro, Manuel Leite, Savonius, Okko, Rugemalira, Emilie, Roine, Irmeli, He, Qiushui, Pelkonen, Tuula
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564843/
https://www.ncbi.nlm.nih.gov/pubmed/32967147
http://dx.doi.org/10.3390/genes11091099
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author Tenhu, Elina
Teräsjärvi, Johanna
Cruzeiro, Manuel Leite
Savonius, Okko
Rugemalira, Emilie
Roine, Irmeli
He, Qiushui
Pelkonen, Tuula
author_facet Tenhu, Elina
Teräsjärvi, Johanna
Cruzeiro, Manuel Leite
Savonius, Okko
Rugemalira, Emilie
Roine, Irmeli
He, Qiushui
Pelkonen, Tuula
author_sort Tenhu, Elina
collection PubMed
description Bacterial meningitis (BM) is a severe disease caused by various bacterial pathogens. Toll-like receptors (TLRs) protect humans from invading pathogens. In this study, we determined whether single nucleotide polymorphisms (SNPs) of TLR4 and TLR9 are associated with susceptibility to and outcome of BM in Angolan children. Samples were taken from 241 patients and 265 age-matched ethnic controls. The SNPs TLR4 rs4986790 (896A > G) and TLR9 rs187084 (−1486T > C) were determined by high-resolution melting analysis (HRMA). The frequency of variant genotypes in TLR4 was significantly higher in patients with Haemophilus influenzae meningitis than controls (odds ratio (OR), 2.5; 95% confidence interval (CI), 1.2–5.4; p = 0.021), whereas the frequency of variant genotypes in TLR9 was significantly lower in patients with H. influenzae meningitis than controls (OR, 0.4; 95% CI, 0.2–0.9; p = 0.036). No such differences were found with other causative pathogens, such as Streptococcus pneumoniae and Neisseria meningitidis. At the time of discharge, patients with meningitis caused by Gram-negative bacteria who were carriers of variant TLR4 genotypes had a higher risk of ataxia (OR, 12.91; 95% CI, 1.52–109.80; p = 0.019) and other neurological sequelae (OR, 11.85; 95% CI, 1.07–131.49; p = 0.044) than those with the wild-type TLR4 genotype. Our study suggests an association between H. influenzae meningitis and genetic variation between TLR4 and TLR9 in Angolan children.
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spelling pubmed-75648432020-10-26 Gene Polymorphisms of TLR4 and TLR9 and Haemophilus influenzae Meningitis in Angolan Children Tenhu, Elina Teräsjärvi, Johanna Cruzeiro, Manuel Leite Savonius, Okko Rugemalira, Emilie Roine, Irmeli He, Qiushui Pelkonen, Tuula Genes (Basel) Article Bacterial meningitis (BM) is a severe disease caused by various bacterial pathogens. Toll-like receptors (TLRs) protect humans from invading pathogens. In this study, we determined whether single nucleotide polymorphisms (SNPs) of TLR4 and TLR9 are associated with susceptibility to and outcome of BM in Angolan children. Samples were taken from 241 patients and 265 age-matched ethnic controls. The SNPs TLR4 rs4986790 (896A > G) and TLR9 rs187084 (−1486T > C) were determined by high-resolution melting analysis (HRMA). The frequency of variant genotypes in TLR4 was significantly higher in patients with Haemophilus influenzae meningitis than controls (odds ratio (OR), 2.5; 95% confidence interval (CI), 1.2–5.4; p = 0.021), whereas the frequency of variant genotypes in TLR9 was significantly lower in patients with H. influenzae meningitis than controls (OR, 0.4; 95% CI, 0.2–0.9; p = 0.036). No such differences were found with other causative pathogens, such as Streptococcus pneumoniae and Neisseria meningitidis. At the time of discharge, patients with meningitis caused by Gram-negative bacteria who were carriers of variant TLR4 genotypes had a higher risk of ataxia (OR, 12.91; 95% CI, 1.52–109.80; p = 0.019) and other neurological sequelae (OR, 11.85; 95% CI, 1.07–131.49; p = 0.044) than those with the wild-type TLR4 genotype. Our study suggests an association between H. influenzae meningitis and genetic variation between TLR4 and TLR9 in Angolan children. MDPI 2020-09-21 /pmc/articles/PMC7564843/ /pubmed/32967147 http://dx.doi.org/10.3390/genes11091099 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Tenhu, Elina
Teräsjärvi, Johanna
Cruzeiro, Manuel Leite
Savonius, Okko
Rugemalira, Emilie
Roine, Irmeli
He, Qiushui
Pelkonen, Tuula
Gene Polymorphisms of TLR4 and TLR9 and Haemophilus influenzae Meningitis in Angolan Children
title Gene Polymorphisms of TLR4 and TLR9 and Haemophilus influenzae Meningitis in Angolan Children
title_full Gene Polymorphisms of TLR4 and TLR9 and Haemophilus influenzae Meningitis in Angolan Children
title_fullStr Gene Polymorphisms of TLR4 and TLR9 and Haemophilus influenzae Meningitis in Angolan Children
title_full_unstemmed Gene Polymorphisms of TLR4 and TLR9 and Haemophilus influenzae Meningitis in Angolan Children
title_short Gene Polymorphisms of TLR4 and TLR9 and Haemophilus influenzae Meningitis in Angolan Children
title_sort gene polymorphisms of tlr4 and tlr9 and haemophilus influenzae meningitis in angolan children
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564843/
https://www.ncbi.nlm.nih.gov/pubmed/32967147
http://dx.doi.org/10.3390/genes11091099
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