A TLR4 polymorphism is associated with asthma and reduced lipopolysaccharide-induced interleukin-12(p70) responses in Swedish children.
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.
Fagerås Böttcher
Malin
M
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
Hmani-Aifa
Mounira
M
Lindström
Anna
A
Jenmalm
Maria Christina
MC
Mai
Xiao-Mei
XM
Nilsson
Lennart
L
Zdolsek
Helena Aniansson
HA
Björkstén
Bengt
B
Söderkvist
Peter
P
Vaarala
Outi
O
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
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