title: CD14 C-159T and toll-like receptor 4 Asp299Gly polymorphisms in surviving meningococcal disease patients.
abstract: BACKGROUND
  Carriage of Neisseria meningitidis occurs approximately in 10% of the population, onset of invasive meningococcal disease (IMD) cannot be predicted and differs between ages. It remains unclear, which host factors determine invasion of the bloodstream by the bacteria. Innate immunity has a very important role in the first recognition of invading pathogens. The functional single nucleotide polymorphisms (SNPs) CD14 C-159T and toll-like receptor 4 (TLR4) Asp299Gly have been associated with the risk of gram-negative infections. However, their role in development of IMD still remains unclear. Our aim was to investigate the influence of CD14 C-159T and TLR4 Asp299Gly polymorphisms on the risk of IMD.
  
  
  RESULTS
  It was a retrospective case control study. Surviving Austrian meningococcal disease patients were enrolled by sending buccal swabs for DNA analysis. 185 cases with a proven meningococcal infection and 770 healthy controls were enrolled. In surviving meningococcal disease patients DNA analysis of CD14 C-159T and TLR 4 Asp299Gly polymorphisms was performed, as they are part of the innate immune response to bacterial determinants. CD14 C-159T and TLR4 Asp299Gly SNPs were not significantly associated with the presence of IMD when compared to healthy controls. The odds ratio for CD14 C-159T SNP was 1.14 (95% confidence interval (CI) 0.91-1.43; p = 0.266). In TLR4 Asp 299 Gly SNP the odds ratio was 0.78 (CI 0.47-1.43; p = 0.359).
  
  
  CONCLUSIONS
  We could not observe a significant influence of CD14 C-159T and TLR4 Asp299Gly polymorphisms on the risk of developing IMD in surviving meningococcal disease patients. To our knowledge, this is the first study investigating the influence of the CD14 C-159T SNP on the susceptibility to IMD.
authors.affiliation: Department of Pediatrics, University Teaching Hospital, Feldkirch, Austria. ariane.biebl@gespag.at
authors.forename: Ariane
authors.initials: A
authors.lastname: Biebl
authors.forename: Axel
authors.initials: A
authors.lastname: Muendlein
authors.forename: Zhyrgal
authors.initials: Z
authors.lastname: Kazakbaeva
authors.forename: Sigrid
authors.initials: S
authors.lastname: Heuberger
authors.forename: Gudrun
authors.initials: G
authors.lastname: Sonderegger
authors.forename: Heinz
authors.initials: H
authors.lastname: Drexel
authors.forename: Susanne
authors.initials: S
authors.lastname: Lau
authors.forename: Renate
authors.initials: R
authors.lastname: Nickel
authors.forename: Michael
authors.initials: M
authors.lastname: Kabesch
authors.forename: Burkhard
authors.initials: B
authors.lastname: Simma
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D005838:Genotype; D006801:Humans; D007113:Immunity, Innate; D007223:Infant; D018950:Lipopolysaccharide Receptors / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D008589:Meningococcal Infections / Q000235:genetics* / Q000378:metabolism*; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D012306:Risk; D051197:Toll-Like Receptor 4 / Q000235:genetics*
chemical_list: D018950:Lipopolysaccharide Receptors; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4