TY - JOUR
T1 - Toll-like receptor 2 as a major gene for asthma in children of European farmers
AU - Eder, Waltraud
AU - Klimecki, Walt
AU - Yu, Lizhi
AU - Von Mutius, Erika
AU - Riedler, Josef
AU - Braun-Fahrländer, Charlotte
AU - Nowak, Dennis
AU - Martinez, Fernando D.
PY - 2004/3
Y1 - 2004/3
N2 - Background: The finding that the prevalence of asthma and allergies Is less frequent in children raised on animal farms has led to the conjecture that exposure to microbial products modifies immune responses. The toll-like receptors (TLRs) represent an evolutionarily conserved family of innate immunity receptors with microbial molecules as ligands. Objectives: We reasoned that polymorphisms in genes encoding TLRs might modulate the protective effects observed in farming populations. Methods: Farmers' and nonfarmers' children living in rural areas in Austria and Germany and who were enrolled in the cross-sectional ALEX study were genotyped for single nucleotide polymorphisms in the TLR2 and TLR4 genes. The frequencies of asthma, allergic rhinitis, and atopic sensitization were compared between the genotypes in relation to exposure to farming and endotoxin. Results: Among farmers' children, those carrying a T allele in TLR2/-16934 compared with children with genotype AA were significantly less likely to have a diagnosis of asthma (3% vs 13%, P = .012), current asthma symptoms (3% vs 16%, P = .004), atopic sensitization (14% vs 27%, P = .023), and current hay fever symptoms (3% vs 14%, P = .01). The association between TLR2/-16934 and asthma among children of farmers was Independent of atopy. No such association was found among children from the same rural communities but not living on farms. Conclusion: Our results suggest that genetic variation in TLR2 is a major determinant of the susceptibility to asthma and allergies in children of farmers.
AB - Background: The finding that the prevalence of asthma and allergies Is less frequent in children raised on animal farms has led to the conjecture that exposure to microbial products modifies immune responses. The toll-like receptors (TLRs) represent an evolutionarily conserved family of innate immunity receptors with microbial molecules as ligands. Objectives: We reasoned that polymorphisms in genes encoding TLRs might modulate the protective effects observed in farming populations. Methods: Farmers' and nonfarmers' children living in rural areas in Austria and Germany and who were enrolled in the cross-sectional ALEX study were genotyped for single nucleotide polymorphisms in the TLR2 and TLR4 genes. The frequencies of asthma, allergic rhinitis, and atopic sensitization were compared between the genotypes in relation to exposure to farming and endotoxin. Results: Among farmers' children, those carrying a T allele in TLR2/-16934 compared with children with genotype AA were significantly less likely to have a diagnosis of asthma (3% vs 13%, P = .012), current asthma symptoms (3% vs 16%, P = .004), atopic sensitization (14% vs 27%, P = .023), and current hay fever symptoms (3% vs 14%, P = .01). The association between TLR2/-16934 and asthma among children of farmers was Independent of atopy. No such association was found among children from the same rural communities but not living on farms. Conclusion: Our results suggest that genetic variation in TLR2 is a major determinant of the susceptibility to asthma and allergies in children of farmers.
KW - Asthma
KW - Atopy
KW - Children
KW - Endotoxin
KW - Farming
KW - Gene-environment interaction
KW - TLR2
KW - TLR4
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UR - http://www.scopus.com/inward/citedby.url?scp=1542721504&partnerID=8YFLogxK
U2 - 10.1016/j.jaci.2003.12.374
DO - 10.1016/j.jaci.2003.12.374
M3 - Article
C2 - 15007351
AN - SCOPUS:1542721504
SN - 0091-6749
VL - 113
SP - 482
EP - 488
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
IS - 3
ER -