title: The effect of polymorphisms at the CD14 promoter and the TLR4 gene on asthma phenotypes in Turkish children with asthma.
abstract: BACKGROUND
  Endotoxin, with its potential to enhance type 1 immunity, is a significant player in the hygiene hypothesis. The combined effects of the genetic variants of various molecules in the endotoxin response pathway on asthma related phenotypes are largely unknown.
  
  
  OBJECTIVE
  To investigate the effects of the genetic variants of CD14 and TLR4 genes on asthma phenotypes in a large number of asthmatic children.
  
  
  METHODS
  613 asthmatic children were genotyped at the CD14-C159T, TLR4-A896G and TLR4-C1196T loci. IgE, eosinophil numbers and FEV1 were compared in 327 children who were not on any controller medications and were symptom free. Multivariate logistic regression was used to determine the factors associated with total IgE.
  
  
  RESULTS
  Among children with atopic asthma, total IgE levels were significantly different among the three genotypes in the co-dominant model [CC: 435 kU/l (interquartile range: 146-820); CT: 361 (140-710); TT 204 (98-435), P = 0.035]. TT genotype was significantly and independently associated with lower IgE levels (OR: 0.5 95%; CI = 0.28-0.90, P = 0.021). Both TLR4-A896G and TLR4-C1196T polymorphisms were more frequent in the mild asthma group with atopy (P = 0.032, 0.018, respectively). The combined effects of the genetic variants in CD14 and TLR4 genes did not improve the observed associations.
  
  
  CONCLUSIONS
  Our study demonstrates that the CD14-C159T promoter variant influences total IgE levels and also indicates that the T allele has a more profound effect on total IgE in children with atopic asthma. Polymorphisms in the TLR4 gene may be associated with milder forms of disease in atopic asthmatics in the population studied.
authors.affiliation: School of Medicine, Pediatric Allergy and Asthma Unit, Hacettepe University, Hacettepe, Ankara, Turkey.
authors.forename: C
authors.initials: C
authors.lastname: Saçkesen
authors.forename: C
authors.initials: C
authors.lastname: Karaaslan
authors.forename: O
authors.initials: O
authors.lastname: Keskin
authors.forename: N
authors.initials: N
authors.lastname: Tokol
authors.forename: F
authors.initials: F
authors.lastname: Tahan
authors.forename: E
authors.initials: E
authors.lastname: Civelek
authors.forename: O U
authors.initials: OU
authors.lastname: Soyer
authors.forename: G
authors.initials: G
authors.lastname: Adalioglu
authors.forename: A
authors.initials: A
authors.lastname: Tuncer
authors.forename: E
authors.initials: E
authors.lastname: Birben
authors.forename: C
authors.initials: C
authors.lastname: Oner
authors.forename: O
authors.initials: O
authors.lastname: Kalayci
mesh_terms: D000293:Adolescent; D001249:Asthma / Q000235:genetics* / Q000503:physiopathology; D002648:Child; D004804:Eosinophils; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000235:genetics; D007073:Immunoglobulin E / Q000097:blood; D018950:Lipopolysaccharide Receptors / Q000235:genetics*; D008297:Male; D010641:Phenotype; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012720:Severity of Illness Index; D051197:Toll-Like Receptor 4 / Q000235:genetics*; D014421:Turkey
chemical_list: D018950:Lipopolysaccharide Receptors; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D007073:Immunoglobulin E