TLR4 gene variants modify endotoxin effects on asthma.
BACKGROUND
Environmental exposure to endotoxin might have a crucial role in immune maturation and development of asthma.


OBJECTIVE
The aim of this study was to investigate whether the effect of endotoxin concentration in settled house dust on asthma is modified by the presence of variation in the TLR4 gene.


METHODS
We performed a cross-sectional study within the German follow-up of the European Community Respiratory Health Survey. Multivariate logistic regression analysis and nonparametric effect estimates (S-Plus) were applied to examine the association between endotoxin exposure and diagnosed asthma, related clinical symptoms, and bronchial hyperreactivity (BHR) stratified for noncarriers and carriers of G299/I399 polymorphism in the TLR4 gene.


RESULTS
In the noncarrier group (n = 279), the prevalence of asthma was significantly increased with elevated endotoxin levels in house dust with adjusted odds ratio 6.24 (95% CI, 1.33-29.17) in the second tertile, and 4.54 (95% CI, 0.94-21.96) in the third tertile compared with the lowest endotoxin tertile. The carriers of the polymorphisms (n = 55) showed a nonsignificant trend to have a lower risk of asthma (crude odds ratio, 0.67; 95% CI, 0.06-8.06 for the second tertile and 1.33; 95% CI, 0.17-10.58 for the third tertile). We found a similar association for wheeze and endotoxin exposure that was also attenuated in subjects with G299/I399 polymorphisms.


CONCLUSIONS
The G299/I399 polymorphisms were associated with a modified response to endotoxin, but the functional relationship still needs clarification.
Werner
Monika
M
Institute of Epidemiology, GSF National Research Center for Environment and Health, Neuherberg, Germany.
Topp
Rebekka
R
Wimmer
Katrin
K
Richter
Kai
K
Bischof
Wolfgang
W
Wjst
Matthias
M
Heinrich
Joachim
J
D000328:Adult; D001249:Asthma / Q000453:epidemiology / Q000235:genetics / Q000503:physiopathology*; D003430:Cross-Sectional Studies; D004391:Dust; D004731:Endotoxins / Q000008:administration & dosage* / Q000032:analysis; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006579:Heterozygote; D006801:Humans; D016017:Odds Ratio; D009994:Osmolar Concentration; D011110:Polymorphism, Genetic; D015995:Prevalence; D012135:Respiratory Sounds / Q000235:genetics; D018570:Risk Assessment
D004391:Dust; D004731:Endotoxins