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). 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.
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). 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.
Authors: Marcin Kurowski; Barbara Majkowska-Wojciechowska; Aleksandra Wardzyńska; Marek L Kowalski Journal: Arch Med Sci Date: 2011-12-30 Impact factor: 3.318
Authors: Remo Frei; Caroline Roduit; Christian Bieli; Susanne Loeliger; Marco Waser; Annika Scheynius; Marianne van Hage; Göran Pershagen; Gert Doekes; Josef Riedler; Erika von Mutius; Felix Sennhauser; Cezmi A Akdis; Charlotte Braun-Fahrländer; Roger P Lauener Journal: PLoS One Date: 2014-03-06 Impact factor: 3.240
Authors: Susanne Bornelöv; Annika Sääf; Erik Melén; Anna Bergström; Behrooz Torabi Moghadam; Ville Pulkkinen; Nathalie Acevedo; Christina Orsmark Pietras; Markus Ege; Charlotte Braun-Fahrländer; Josef Riedler; Gert Doekes; Michael Kabesch; Marianne van Hage; Juha Kere; Annika Scheynius; Cilla Söderhäll; Göran Pershagen; Jan Komorowski Journal: PLoS One Date: 2013-11-19 Impact factor: 3.240