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Common polymorphisms in the complement system and susceptiblity to bacterial meningitis

Adriani, Kirsten S., Brouwer, Matthijs C., Geldhoff, Madelijn, Baas, Frank, Zwinderman, Aeilko H., Morgan, Bryan Paul ORCID:, Harris, Claire Louise, van der Ende, Arie and van de Beek, Diederik 2013. Common polymorphisms in the complement system and susceptiblity to bacterial meningitis. Journal of Infection 66 (3) , pp. 255-262. 10.1016/j.jinf.2012.10.008

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Objective Risk factors for susceptibility to bacterial meningitis have been identified, but basic causes of inter-individual differences in susceptibility are largely unknown. Methods To determine the effect of genetic variation in the complement system on susceptibility to bacterial meningitis we performed a prospective nationwide genetic association study in patients with community-acquired bacterial meningitis. We genotyped 17 common SNPs (minor allele frequencies >5%) in genes coding for complement components and evaluated functional consequences by measuring complement levels in the cerebrospinal fluid. Results From March 2006 to June 2009 we included 636 adults with community-acquired bacterial meningitis. DNA was available for 439 patients and 302 controls. Rs1047286 (Pro314Leu) in complement component 3 was associated with reduced susceptibility to bacterial meningitis after correction for multiple testing: the protective Leu/Leu genotype was found in 5 of 435 patients (1%) compared to 15 of 302 controls (5%; odds ratio [OR] 4.50, 95% confidence interval [CI] 1.62–12.50, p = 0.0017). Rs1047286 is in strong linkage disequilibrium with Rs2230199 (C3 Arg102Gly), of which the Arg/Arg genotype was associated with higher CSF levels of C3 and lower levels of C5a and terminal complement complex (TCC; soluble C5b-9), indicating decreased consumption of C3 and less activation of the complement system. Rs1047286 was associated with susceptibility albeit not significantly after Bonferroni correction (OR 1.37, 95% CI 1.01–1.87; p = 0.04). Conclusions This study shows an association between a common single nucleotide polymorphism in C3 and susceptibility for community-acquired bacterial meningitis.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: R Medicine > R Medicine (General)
Uncontrolled Keywords: bacterial meningitis, complement system, common polymorphisms, SNPs, S. pneumoniae
Publisher: Elsevier
ISSN: 0163-4453
Last Modified: 21 Oct 2022 10:43

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