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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, 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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Abstract

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: 04 Jun 2017 04:34
URI: http://orca-mwe.cf.ac.uk/id/eprint/41118

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