A polymorphism in CD14 modifies the effect of farm milk consumption on allergic diseases and CD14 gene expression.
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.
Bieli
Christian
C
Institute of Social and Preventive Medicine, University of Basel, Basel, Switzerland. christian.bieli@unibas.ch
Eder
Waltraud
W
Frei
Remo
R
Braun-Fahrländer
Charlotte
C
Klimecki
Walt
W
Waser
Marco
M
Riedler
Josef
J
von Mutius
Erika
E
Scheynius
Annika
A
Pershagen
Göran
G
Doekes
Gert
G
Lauener
Roger
R
Martinez
Fernando D
FD
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
D018950:Lipopolysaccharide Receptors; D006147:Guanine; D000225:Adenine