title: A TLR4 polymorphism is associated with asthma and reduced lipopolysaccharide-induced interleukin-12(p70) responses in Swedish children.
abstract: BACKGROUND
  Bacterial signals play an important role in the maturation of the immune system. Polymorphisms in genes coding for receptors to bacterial components can alter the immune responsiveness of the host to microbial agents and may indicate the development of aberrant immune responses that are associated with immune-mediated diseases such as atopic diseases.
  
  
  OBJECTIVE
  The study's objective was to investigate the relationship between TLR4 and CD14 gene polymorphisms, the LPS responsiveness of PBMCs, and the presence of asthma and allergic rhinoconjunctivitis in children.
  
  
  METHODS
  The TLR4 (Asp299Gly) and CD14/-159 polymorphisms were determined in 115 Swedish children aged 8 and 14 years. LPS-induced IL-12(p70), IL-10, and IFN-gamma responses of PBMCs from 69 of the children were analyzed by means of ELISA. The levels of soluble CD14 in serum samples were analyzed by means of ELISA, and the total IgE levels were analyzed by means of UniCAP Total IgE (Pharmacia Diagnostics, Uppsala, Sweden).
  
  
  RESULTS
  Decreased LPS-induced IL-12(p70) and IL-10 responses were associated with the TLR4 (Asp299Gly) polymorphism and independently with asthma, especially atopic asthma. The TLR4 (Asp299Gly) polymorphism was associated with a 4-fold higher prevalence of asthma in school-aged children (adjusted odds ratio 4.5, 95% CI 1.1-17.4) but not to allergic rhinoconjunctivitis.
  
  
  CONCLUSIONS
  A TLR4 polymorphism modifies innate immune responses in children and may be an important determinant for the development of asthma. This may influence the outcome of intervention studies that use microbial stimuli as immune modulators.
authors.affiliation: Division of Pediatrics, Department of Molecular and Clinical Medicine, and Clinical Research Centre, Faculty of Health Sciences, Linköping University, 85 Linköping, Sweden. MalFa@imk.liu.se
authors.forename: Malin
authors.initials: M
authors.lastname: Fagerås Böttcher
authors.forename: Mounira
authors.initials: M
authors.lastname: Hmani-Aifa
authors.forename: Anna
authors.initials: A
authors.lastname: Lindström
authors.forename: Maria Christina
authors.initials: MC
authors.lastname: Jenmalm
authors.forename: Xiao-Mei
authors.initials: XM
authors.lastname: Mai
authors.forename: Lennart
authors.initials: L
authors.lastname: Nilsson
authors.forename: Helena Aniansson
authors.initials: HA
authors.lastname: Zdolsek
authors.forename: Bengt
authors.initials: B
authors.lastname: Björkstén
authors.forename: Peter
authors.initials: P
authors.lastname: Söderkvist
authors.forename: Outi
authors.initials: O
authors.lastname: Vaarala
mesh_terms: D000293:Adolescent; D001249:Asthma / Q000235:genetics* / Q000276:immunology; D002648:Child; D003233:Conjunctivitis, Allergic / Q000235:genetics / Q000276:immunology; D020022:Genetic Predisposition to Disease; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D018664:Interleukin-12 / Q000097:blood*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000097:blood / Q000235:genetics; D008070:Lipopolysaccharides / Q000276:immunology*; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D021122:Protein Subunits / Q000097:blood*; D011956:Receptors, Cell Surface / Q000235:genetics*; D006255:Rhinitis, Allergic, Seasonal / Q000235:genetics / Q000276:immunology; D013548:Sweden; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
chemical_list: D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D021122:Protein Subunits; D011956:Receptors, Cell Surface; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D016753:Interleukin-10; D018664:Interleukin-12; D007073:Immunoglobulin E