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Bacterial meningitis (BM) is a serious infection of the central nervous system, frequently occurring in childhood and often resulting in hearing loss, learning disabilities, and encephalopathy. Previous studies showed that genetic variation in innate immune response genes affects susceptibility, severity, and outcome of BM. The aim of this study is to describe whether single nucleotide polymorphisms (SNPs) in pathogen recognition gene products are associated with susceptibility to develop BM in single genes analysis as well as SNP combinations. Genotype frequencies of seven SNPs, in five immune response genes encoding for Toll-like receptors (TLRs), nucleotide oligomerization domain (NOD) proteins and caspase-1 (CASP1), in 391 children with meningococcal meningitis (MM) and 82 children with pneumococcal meningitis were compared with a large cohort of 1141 ethnically matched healthy controls. Carriage of  TLR4  +896 GG mutant predisposed to susceptibility to develop MM ( p  = 1.2*10 −5 , OR  = 9.4, 95% CI  = 3.0–29.2). The  NOD2  SNP8 mutant was significantly more frequent in MM patients compared to controls ( p  = 0.0004, OR  = 12.2, 95% CI  = 2.6–57.8). Combined carriage of  TLR2  +2477 and  TLR4  +896 mutants was strongly associated with MM ( p  = 4.2*10 −5 , OR  = 8.6, 95% CI  = 2.7–27.3). A carrier trait of  TLR4  +896 and  NOD2  SNP8 mutants was also strongly associated with susceptibility to develop MM ( p  = 4.2*10 −5 , OR  = 10.6, 95% CI  = 2.9–38.6). This study associates SNPs in  TLR4  and  NOD2  with susceptibility to develop MM.

plos one

Single Nucleotide Polymorphisms in Pathogen Recognition Receptor Genes Are Associated with Susceptibility to Meningococcal Meningitis in a Pediatric Cohort