title: A polymorphism in CD14 modifies the effect of farm milk consumption on allergic diseases and CD14 gene expression.
abstract: BACKGROUND
  Consumption of farm milk in early life is associated with less asthma and allergies.
  
  
  OBJECTIVE
  We hypothesized that genetic variation in the innate immunity receptor CD14 might modify the association between farm milk consumption and asthma and atopy.
  
  
  METHODS
  Questionnaire data, serum IgE levels, and genotypes for 4 single nucleotide polymorphisms in CD14 were assessed in farmers' and nonfarmers' children from 2 European populations (Allergy and Endotoxin study, n = 576; Prevention of Allergy Risk factors for Sensitization in children related to Farming and Anthroposophic Lifestyle study, n = 1539). In a subsample (n = 222) CD14 gene expression was measured in peripheral blood leukocytes. The effects of farm milk and CD14 genotypes on asthma, allergies, and CD14 expression and their interactions were investigated.
  
  
  RESULTS
  We found a significant interaction between genetic variation in CD14/-1721 and farm milk consumption. Adjusted odds ratios for the association between farm milk and asthma varied between the genotypes: AA, 0.18 (95% CI, 0.07-0.47); AG, 0.47 (95% CI, 0.26-0.86); and GG, 0.98 (95% CI, 0.46-2.08). Similar patterns were observed for symptoms of allergic rhinoconjunctivitis and pollen sensitization. CD14/-1721 also modified the association between farm milk and CD14 gene expression (adjusted geometric means ratios: AA, 1.61 (95% CI, 0.98-2.66); AG, 1.11 (95% CI, 0.71-1.72); and GG, 0.76 (95% CI, 0.39-1.48).
  
  
  CONCLUSIONS
  The protective effect of farm milk consumption on allergic diseases is stronger in children carrying the A allele in CD14/-1721 than in children homozygous for the G allele. This might be mediated through farm milk-induced upregulated CD14 gene expression.
  
  
  CONCLUSIONS
  Our results support the hypothesis that the inverse association between farm milk consumption and allergic diseases is mediated by CD14-activated innate immune mechanisms.
authors.affiliation: Institute of Social and Preventive Medicine, University of Basel, Basel, Switzerland. christian.bieli@unibas.ch
authors.forename: Christian
authors.initials: C
authors.lastname: Bieli
authors.forename: Waltraud
authors.initials: W
authors.lastname: Eder
authors.forename: Remo
authors.initials: R
authors.lastname: Frei
authors.forename: Charlotte
authors.initials: C
authors.lastname: Braun-Fahrländer
authors.forename: Walt
authors.initials: W
authors.lastname: Klimecki
authors.forename: Marco
authors.initials: M
authors.lastname: Waser
authors.forename: Josef
authors.initials: J
authors.lastname: Riedler
authors.forename: Erika
authors.initials: E
authors.lastname: von Mutius
authors.forename: Annika
authors.initials: A
authors.lastname: Scheynius
authors.forename: Göran
authors.initials: G
authors.lastname: Pershagen
authors.forename: Gert
authors.initials: G
authors.lastname: Doekes
authors.forename: Roger
authors.initials: R
authors.lastname: Lauener
authors.forename: Fernando D
authors.initials: FD
authors.lastname: Martinez
mesh_terms: D000225:Adenine / Q000096:biosynthesis; D000483:Alleles; D000818:Animals; D002648:Child; D003430:Cross-Sectional Studies; D003612:Dairying; D005260:Female; D005512:Food Hypersensitivity / Q000235:genetics* / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology*; D005838:Genotype; D006147:Guanine / Q000096:biosynthesis; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D007223:Infant; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis* / Q000235:genetics*; D008297:Male; D008892:Milk / Q000276:immunology*; D020641:Polymorphism, Single Nucleotide
chemical_list: D018950:Lipopolysaccharide Receptors; D006147:Guanine; D000225:Adenine