Polymorphisms in Toll-like receptors 2, 4, and 9 are highly associated with hearing loss in survivors of bacterial meningitis

Genetic variation in innate immune response genes contributes to inter-individual differences in disease manifestation and degree of complications upon infection. We recently described an association of single nucleotide polymorphisms (SNPs) in TLR9 with susceptibility to meningococcal meningitis (M...

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Bibliographic Details
Published in:PloS one 2012-05, Vol.7 (5), p.e35837-e35837
Main Authors: van Well, Gijs Th J, Sanders, Marieke S, Ouburg, Sander, van Furth, A Marceline, Morré, Servaas A
Format: Article
Language:English
Subjects:
Age
Alleles
Analysis
Apoptosis
Bacteria
Bacterial meningitis
Biology
Central nervous system
Child
Child, Preschool
Children
Chromosomes
Cochlea
Complications
Cytokines
Dendritic cells
Female
Gene Frequency
Gene mutation
Genes
Genetic aspects
Genetic diversity
Genetic markers
Genetic Predisposition to Disease
Genomics
Genotype
Gram-positive bacteria
Haemophilus influenzae
Hearing loss
Hearing Loss - complications
Hearing Loss - genetics
Helicobacter pylori
Humans
Immune response
Immune system
Immunology
Infant
Infant, Newborn
Infection
Infectious diseases
Inflammation
Innate immunity
Laboratories
Male
Medicine
Meningitis
Meningitis, Bacterial - complications
Mortality
Neisseria meningitidis
Nod1 protein
NOD2 protein
Patients
Pediatrics
Polymorphism, Single Nucleotide
Proteins
Public health
Receptors
Rheumatology
Risk
Risk groups
Sepsis
Single nucleotide polymorphisms
Single-nucleotide polymorphism
Streptococcus infections
Streptococcus pneumoniae
Studies
Survivors
Therapeutic applications
TLR2 protein
TLR4 protein
TLR9 protein
Toll-Like Receptor 2 - genetics
Toll-Like Receptor 4 - genetics
Toll-Like Receptor 9 - genetics
Toll-like receptors
Tumor necrosis factor-TNF
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Summary:Genetic variation in innate immune response genes contributes to inter-individual differences in disease manifestation and degree of complications upon infection. We recently described an association of single nucleotide polymorphisms (SNPs) in TLR9 with susceptibility to meningococcal meningitis (MM). In this study, we investigate the association of SNPs in multiple pathogen recognition and immune response genes with clinical features that determine severity and outcome (especially hearing loss) of childhood MM and pneumococcal meningitis (PM). Eleven SNPs in seven genes (TLR2, TLR4, TLR9, NOD1, NOD2, CASP1, and TRAIL) were genotyped in 393 survivors of childhood bacterial meningitis (BM) (327 MM patients and 66 PM patients). Genotype distributions of single SNPs and combination of SNPs were compared between thirteen clinical characteristics associated with severity of BM. After correction for multiple testing, TLR4+896 mutant alleles were highly associated with post-meningitis hearing loss, especially MM (p= 0.001, OR 4.0 for BM, p= 0.0004, OR 6.2 for MM). In a multigene analysis, combined carriership of the TLR2+2477 wild type (WT) with TLR4+896 mutant alleles increases the risk of hearing loss (p
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0035837