Mechanisms of AllergyToll-like receptor 2 as a major gene for asthma in children of European farmers☆
Section snippets
Population, phenotypes, and exposure to farming and endotoxin
Our study population included 609 children in school grades 1 to 6 from rural areas in Austria and Bavaria (Germany) who took part in the cross-sectional ALEX study, as previously described.8 In brief, a self-administered questionnaire on respiratory and allergic diseases was filled out by the parents of children living on a farm and the parents of children living in the same rural area but not raised on a farm. Participating children and their parents were asked for consent to venipuncture and
Results
Our study population included 229 farmers' children and 380 children from the same rural area but not living on a farm. The mean age was 9.4 years (SD, 1.5) in farmers' children and 9.3 years (SD, 1.5) in nonfarmers' children. There were slightly more boys among the farmers' children (56%) than among the nonfarmers' children (51%).
The median of the endotoxin concentrations from the mattress samples was 27.4 EU/mg dust (interquartile range, 24.0 EU/mg) and, as previously reported,13 was
Discussion
In this study we found that a polymorphism in the TLR2 gene is strongly associated with the frequency of asthma and allergies in children of European farmers and that a polymorphism in the TLR4 gene has an influence on atopy in children heavily exposed to endotoxin. These results point to a gene-by-environment interaction because both TLR2 and TLR4 are genes encoding ancient pattern-recognition receptors for different microbial molecules.
The potential role of TLRs as regulators of immune
Acknowledgements
We thank Cathy Holberg for statistical support and the collaborators of the ALEX Team: Soyoun Maisch, Rudi Schierl, David Carr (Munich, Germany), Marco Waser (Basel, Switzerland), Roger Lauener, Felix Sennhauser (Zurich, Switzerland), Mynda Schreuer, Gerd Oberfeld (Salzburg, Austria), Harald Renz, Udo Herz (Marburg Germany), Albrecht Bufe (Bochum, Germany), and Otto Holst (Borstel, Germany).
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Supported by the National Heart, Lung, and Blood Institute (PGA-HL66800 and a Specialized Center of Research grant: HL67672), by the Bavarian Ministry for the Environment, by an Austrian grant from the Health Department of the Government of Salzburg, by the Zürich Lung Association, and by the United Bank of Switzerland.
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Reprint requests: Fernando D. Martinez, MD, Arizona Respiratory Center, University of Arizona, 1501 N Campbell Ave, PO Box 245030, Tucson, AZ 85724.