Association of polymorphisms of toll-like receptor 4 with a reduced prevalence of hay fever and atopy.
BACKGROUND
The response to innate immune stimuli seems to be critical to conditioning adaptive immunity. Early exposure to endotoxin initiates immune responses that have been shown to alter the risk of asthma and allergic diseases. The toll-like receptor 4 (TLR4) gene encodes the principal innate immunity receptor in humans for bacterial endotoxin. Polymorphisms in the TLR4 gene may regulate the effects of endotoxin exposure and could play a role in the development of asthma and atopy-related phenotypes.


OBJECTIVE
To investigate the association between TLR4 polymorphisms and allergic phenotypes in nonsmokers.


METHODS
The data from 915 nonsmoking students were available for the study. The TLR4 299 and 399 polymorphisms were genotyped using mouthwash samples. The TLR4 299 and 399 polymorphisms were grouped together to define the TLR4 polymorphic group. Skin prick tests were conducted in a subgroup of healthy participants. A brief questionnaire was administered to determine demographic characteristics and chronic health conditions.


RESULTS
The prevalence of hay fever was 0% in the TLR4 polymorphic group and 7.5% in the wild-type group (P = .01). After controlling for age group and sex using logistic regression, the odds of having hay fever were reduced by 88% (P = .009) in the TLR4 polymorphic group compared with the wild-type group. In a subgroup analysis, the association between TLR4 polymorphisms and atopy was only observed among females.


CONCLUSIONS
To our knowledge, this study is the first to report an association between TLR4 polymorphisms and atopy-related phenotypes in a nonsmoking population. Further investigation of the role of TLR4 polymorphisms in asthma and atopy-related phenotypes is warranted.
Senthilselvan
Ambikaipakan
A
Department of Public Health Sciences, School of Public Health, University of Alberta, Edmonton, Alberta, Canada. sentil@ualberta.ca
Rennie
Donna
D
Chénard
Liliane
L
Burch
Lauranell H
LH
Babiuk
Lorne
L
Schwartz
David A
DA
Dosman
James A
JA
D000293:Adolescent; D000328:Adult; D000485:Allergens / Q000276:immunology; D005260:Female; D005787:Gene Frequency; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology; D008297:Male; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D006255:Rhinitis, Allergic, Seasonal / Q000453:epidemiology / Q000235:genetics*; D012737:Sex Factors; D012882:Skin Tests; D051197:Toll-Like Receptor 4 / Q000235:genetics*
D000485:Allergens; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4