Toll-like receptor 2 as a major gene for asthma in children of European farmers.
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.


OBJECTIVE
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.


CONCLUSIONS
Our results suggest that genetic variation in TLR2 is a major determinant of the susceptibility to asthma and allergies in children of farmers.
Arizona Respiratory Center, University of Arizona, Tucson 85724, USA.
Waltraud
W
Eder
Walt
W
Klimecki
Lizhi
L
Yu
Erika
E
von Mutius
Josef
J
Riedler
Charlotte
C
Braun-Fahrländer
Dennis
D
Nowak
Fernando D
FD
Martinez
D000328:Adult; D000383:Agriculture; D001249:Asthma / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology*; D001317:Austria / Q000453:epidemiology; D001483:Base Sequence; D016022:Case-Control Studies; D002648:Child; D003430:Cross-Sectional Studies; D004247:DNA / Q000235:genetics; D004731:Endotoxins / Q000494:pharmacology; D005260:Female; D005858:Germany / Q000453:epidemiology; D006801:Humans; D006967:Hypersensitivity / Q000453:epidemiology / Q000235:genetics / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D010641:Phenotype; D011110:Polymorphism, Genetic; D011956:Receptors, Cell Surface / Q000235:genetics*; D012424:Rural Population; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D004731:Endotoxins; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D004247:DNA