Kirsten S Adriani, Matthijs C Brouwer, Madelijn Geldhoff, Frank Baas, Aeilko H Zwinderman, B Paul Morgan, Claire L Harris, Arie van der Ende, Diederik van de Beek
Department of Neurology, Center of Infection and Immunity Amsterdam-CINIMA, Academic Medical Center, University of Amsterdam, PO Box 22660, 1100DD Amsterdam, The Netherlands.
The Journal of infection 2013 MarRisk factors for susceptibility to bacterial meningitis have been identified, but basic causes of inter-individual differences in susceptibility are largely unknown. 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. 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). This study shows an association between a common single nucleotide polymorphism in C3 and susceptibility for community-acquired bacterial meningitis. Copyright © 2012 The British Infection Association. Published by Elsevier Ltd. All rights reserved.
Kirsten S Adriani, Matthijs C Brouwer, Madelijn Geldhoff, Frank Baas, Aeilko H Zwinderman, B Paul Morgan, Claire L Harris, Arie van der Ende, Diederik van de Beek. Common polymorphisms in the complement system and susceptiblity to bacterial meningitis. The Journal of infection. 2013 Mar;66(3):255-62
PMID: 23068452
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