A polymorphism in CD14 modifies the effect of farm milk consumption on allergic diseases and CD14 gene expression

作者：Bieli Christian^*; Eder Waltraud; Frei Remo; Braun Fahrlaender Charlotte; Klimecki Walt; Waser Marco; Riedler Josef; von Mutius Erika; Scheynius Annika; Pershagen Goran; Doekes Gert; Lauener Roger; Martinez Fernando D

来源：Journal of Allergy and Clinical Immunology, 2007, 120(6): 1308-1315.

DOI：10.1016/j.jaci.2007.07.034

• allergy
• asthma
• CD14
• gene-environment interaction
• gene expression
• farming
• epidemiology

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, I. 11 (95% CI, 0.71-1.72); and GG, 0.76 (95% CI, 0.39-1.48).
Conclusion: 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.
Clinical implications: Our results support the hypothesis that the inverse association between farm milk consumption and allergic diseases is mediated by CD14-activated innate immune mechanisms.

• 出版日期2007-12