Genetic variation in the β2-adrenocepter gene is associated with susceptibility to bacterial meningitis in adults.

Recently, the biased β2-adrenoceptor/β-arrestin pathway was shown to play a pivotal role in crossing of the blood brain barrier by Neisseria meningitidis. We hypothesized that genetic variation in the β2-adrenoceptor gene (ADRB2) may influence susceptibility to bacterial meningitis. In a prospective...

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Autores principales:	Kirsten S Adriani, Matthijs C Brouwer, Frank Baas, Aeilko H Zwinderman, Arie van der Ende, Diederik van de Beek
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2faff4bf605d4750a206b16a451db838
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spelling	oai:doaj.org-article:2faff4bf605d4750a206b16a451db8382021-11-18T07:18:05ZGenetic variation in the β2-adrenocepter gene is associated with susceptibility to bacterial meningitis in adults.1932-620310.1371/journal.pone.0037618https://doaj.org/article/2faff4bf605d4750a206b16a451db8382012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22624056/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Recently, the biased β2-adrenoceptor/β-arrestin pathway was shown to play a pivotal role in crossing of the blood brain barrier by Neisseria meningitidis. We hypothesized that genetic variation in the β2-adrenoceptor gene (ADRB2) may influence susceptibility to bacterial meningitis. In a prospective genetic association study we genotyped 542 patients with CSF culture proven community acquired bacterial meningitis and 376 matched controls for 2 functional single nucleotide polymorphisms in the β2-adrenoceptor gene (ADRB2). Furthermore, we analyzed if the use of non-selective beta-blockers, which bind to the β2-adrenoceptor, influenced the risk of bacterial meningitis. We identified a functional polymorphism in ADRB2 (rs1042714) to be associated with an increased risk for bacterial meningitis (Odds ratio [OR] 1.35, 95% confidence interval [CI] 1.04-1.76; p = 0.026). The association remained significant after correction for age and was more prominent in patients with pneumococcal meningitis (OR 1.52, 95% CI 1.12-2.07; p = 0.007). For meningococcal meningitis the difference in genotype frequencies between patients and controls was similar to that in pneumococcal meningitis, but this was not statistically significant (OR 1.43, 95% CI 0.60-3.38; p = 0.72). Patients with bacterial meningitis had a lower frequency of non-selective beta-blockers use compared to the age matched population (0.9% vs. 1.8%), although this did not reach statistical significance (OR 1.96 [95% CI 0.88-4.39]; p = 0.09). In conclusion, we identified an association between a genetic variant in the β2-adrenoceptor and increased susceptibility to bacterial meningitis. The potential benefit of pharmacological treatment targeting the β2-adrenoceptor to prevent bacterial meningitis in the general population or patients with bacteraemia should be further studied in both experimental studies and observational cohorts.Kirsten S AdrianiMatthijs C BrouwerFrank BaasAeilko H ZwindermanArie van der EndeDiederik van de BeekPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 5, p e37618 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kirsten S Adriani Matthijs C Brouwer Frank Baas Aeilko H Zwinderman Arie van der Ende Diederik van de Beek Genetic variation in the β2-adrenocepter gene is associated with susceptibility to bacterial meningitis in adults.
description	Recently, the biased β2-adrenoceptor/β-arrestin pathway was shown to play a pivotal role in crossing of the blood brain barrier by Neisseria meningitidis. We hypothesized that genetic variation in the β2-adrenoceptor gene (ADRB2) may influence susceptibility to bacterial meningitis. In a prospective genetic association study we genotyped 542 patients with CSF culture proven community acquired bacterial meningitis and 376 matched controls for 2 functional single nucleotide polymorphisms in the β2-adrenoceptor gene (ADRB2). Furthermore, we analyzed if the use of non-selective beta-blockers, which bind to the β2-adrenoceptor, influenced the risk of bacterial meningitis. We identified a functional polymorphism in ADRB2 (rs1042714) to be associated with an increased risk for bacterial meningitis (Odds ratio [OR] 1.35, 95% confidence interval [CI] 1.04-1.76; p = 0.026). The association remained significant after correction for age and was more prominent in patients with pneumococcal meningitis (OR 1.52, 95% CI 1.12-2.07; p = 0.007). For meningococcal meningitis the difference in genotype frequencies between patients and controls was similar to that in pneumococcal meningitis, but this was not statistically significant (OR 1.43, 95% CI 0.60-3.38; p = 0.72). Patients with bacterial meningitis had a lower frequency of non-selective beta-blockers use compared to the age matched population (0.9% vs. 1.8%), although this did not reach statistical significance (OR 1.96 [95% CI 0.88-4.39]; p = 0.09). In conclusion, we identified an association between a genetic variant in the β2-adrenoceptor and increased susceptibility to bacterial meningitis. The potential benefit of pharmacological treatment targeting the β2-adrenoceptor to prevent bacterial meningitis in the general population or patients with bacteraemia should be further studied in both experimental studies and observational cohorts.
format	article
author	Kirsten S Adriani Matthijs C Brouwer Frank Baas Aeilko H Zwinderman Arie van der Ende Diederik van de Beek
author_facet	Kirsten S Adriani Matthijs C Brouwer Frank Baas Aeilko H Zwinderman Arie van der Ende Diederik van de Beek
author_sort	Kirsten S Adriani
title	Genetic variation in the β2-adrenocepter gene is associated with susceptibility to bacterial meningitis in adults.
title_short	Genetic variation in the β2-adrenocepter gene is associated with susceptibility to bacterial meningitis in adults.
title_full	Genetic variation in the β2-adrenocepter gene is associated with susceptibility to bacterial meningitis in adults.
title_fullStr	Genetic variation in the β2-adrenocepter gene is associated with susceptibility to bacterial meningitis in adults.
title_full_unstemmed	Genetic variation in the β2-adrenocepter gene is associated with susceptibility to bacterial meningitis in adults.
title_sort	genetic variation in the β2-adrenocepter gene is associated with susceptibility to bacterial meningitis in adults.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/2faff4bf605d4750a206b16a451db838
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Genetic variation in the β2-adrenocepter gene is associated with susceptibility to bacterial meningitis in adults.

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