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

Christian Bieli, Waltraud Eder, Remo Frei, Charlotte Braun-Fahrländer, Walter Klimecki, Marco Waser, Josef Riedler, Erika von Mutius, Annika Scheynius, Göran Pershagen, Gert Doekes, Roger Lauener, Fernando Martinez

Research output: Contribution to journalArticle

74 Citations (Scopus)

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). 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.

Original languageEnglish (US)
Pages (from-to)1308-1315
Number of pages8
JournalJournal of Allergy and Clinical Immunology
Volume120
Issue number6
DOIs
StatePublished - Dec 2007

Fingerprint

Milk
Gene Expression
Hypersensitivity
Asthma
Genotype
Alleles
Farms
Pollen
Agriculture
Innate Immunity
Endotoxins
Immunoglobulin E
Single Nucleotide Polymorphism
Life Style
Leukocytes
Odds Ratio
Serum
Population

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

A polymorphism in CD14 modifies the effect of farm milk consumption on allergic diseases and CD14 gene expression. / Bieli, Christian; Eder, Waltraud; Frei, Remo; Braun-Fahrländer, Charlotte; Klimecki, Walter; Waser, Marco; Riedler, Josef; von Mutius, Erika; Scheynius, Annika; Pershagen, Göran; Doekes, Gert; Lauener, Roger; Martinez, Fernando.

In: Journal of Allergy and Clinical Immunology, Vol. 120, No. 6, 12.2007, p. 1308-1315.

Research output: Contribution to journalArticle

Bieli, C, Eder, W, Frei, R, Braun-Fahrländer, C, Klimecki, W, Waser, M, Riedler, J, von Mutius, E, Scheynius, A, Pershagen, G, Doekes, G, Lauener, R & Martinez, F 2007, 'A polymorphism in CD14 modifies the effect of farm milk consumption on allergic diseases and CD14 gene expression', Journal of Allergy and Clinical Immunology, vol. 120, no. 6, pp. 1308-1315. https://doi.org/10.1016/j.jaci.2007.07.034
Bieli, Christian ; Eder, Waltraud ; Frei, Remo ; Braun-Fahrländer, Charlotte ; Klimecki, Walter ; Waser, Marco ; Riedler, Josef ; von Mutius, Erika ; Scheynius, Annika ; Pershagen, Göran ; Doekes, Gert ; Lauener, Roger ; Martinez, Fernando. / A polymorphism in CD14 modifies the effect of farm milk consumption on allergic diseases and CD14 gene expression. In: Journal of Allergy and Clinical Immunology. 2007 ; Vol. 120, No. 6. pp. 1308-1315.
@article{05da06aa588740aa8661ab147df5acc2,
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). 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.",
keywords = "Allergy, asthma, CD14, epidemiology, farming, gene expression, gene-environment interaction",
author = "Christian Bieli and Waltraud Eder and Remo Frei and Charlotte Braun-Fahrl{\"a}nder and Walter Klimecki and Marco Waser and Josef Riedler and {von Mutius}, Erika and Annika Scheynius and G{\"o}ran Pershagen and Gert Doekes and Roger Lauener and Fernando Martinez",
year = "2007",
month = "12",
doi = "10.1016/j.jaci.2007.07.034",
language = "English (US)",
volume = "120",
pages = "1308--1315",
journal = "Journal of Allergy and Clinical Immunology",
issn = "0091-6749",
publisher = "Mosby Inc.",
number = "6",

}

TY - JOUR

T1 - A polymorphism in CD14 modifies the effect of farm milk consumption on allergic diseases and CD14 gene expression

AU - Bieli, Christian

AU - Eder, Waltraud

AU - Frei, Remo

AU - Braun-Fahrländer, Charlotte

AU - Klimecki, Walter

AU - Waser, Marco

AU - Riedler, Josef

AU - von Mutius, Erika

AU - Scheynius, Annika

AU - Pershagen, Göran

AU - Doekes, Gert

AU - Lauener, Roger

AU - Martinez, Fernando

PY - 2007/12

Y1 - 2007/12

N2 - 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.

AB - 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.

KW - Allergy

KW - asthma

KW - CD14

KW - epidemiology

KW - farming

KW - gene expression

KW - gene-environment interaction

UR - http://www.scopus.com/inward/record.url?scp=36749022933&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=36749022933&partnerID=8YFLogxK

U2 - 10.1016/j.jaci.2007.07.034

DO - 10.1016/j.jaci.2007.07.034

M3 - Article

C2 - 17919709

AN - SCOPUS:36749022933

VL - 120

SP - 1308

EP - 1315

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

SN - 0091-6749

IS - 6

ER -