Association of Toll-like receptor 4 alleles with symptoms and sensitization to laboratory animals.
BACKGROUND
Researchers and technicians working with laboratory animals (LAs) are exposed to animal allergen and endotoxin, which can interact to potentiate or inhibit symptoms or allergic responses. We hypothesized that functional genetic variants of Toll-like receptor 4 (TLR4), a key surface receptor for endotoxin, interface between worker and workplace and affect animal sensitization, symptoms, or both.


OBJECTIVE
We sought to determine whether TLR4/8551 variants alter the risk for LA sensitization, symptoms, or both.


METHODS
Three hundred thirty-five researchers, 195 of whom worked with animals, completed questions on workplace practices and symptoms and underwent skin prick tests or RASTs to common and animal allergens. Real-time PCR assessed TLR4/8551 and TLR4/8851 variants. Nominal logistic regression was used to analyze the contribution of demographic, exposure, and genetic variables to outcomes of interest.


RESULTS
Twenty-one percent of workers were LA sensitized, and 29% reported 1 or more symptoms to LAs. The TLR4/8551 G variant, which is less responsive to endotoxin, was detected in 9% and in linkage disequilibrium with the TLR4/8851 T allele. The G variant significantly associated with atopy and LA sensitization. Workers with the G variant spent significantly longer hours in high endotoxin/animal allergen tasks compared with those with the AA variant, which is perhaps less affected by endotoxin exposures. In multivariate analyses the G variant and longer animal research hours increased the risk of LA sensitization. Job tasks and LA sensitization, but not TLR4 variants, were predictors of LA-induced symptoms.


CONCLUSIONS
Workers with TLR4 variants that reduce responsiveness to endotoxin have higher risks for LA and other allergen sensitization but spend longer hours in tasks with high endotoxin and animal allergen exposures.
Division of Environmental and Occupational Health Sciences, Department of Medicine, National Jewish Medical and Research Center, Denver, CO 80206, USA. pachecok@njc.org
Karin
K
Pacheco
Lisa
L
Maier
Lori
L
Silveira
Kelly
K
Goelz
Kristyn
K
Noteware
Bevin
B
Luna
Ron
R
du Bois
Jim
J
Murphy
Cecile
C
Rose
D000293:Adolescent; D000328:Adult; D000483:Alleles; D000485:Allergens / Q000032:analysis / Q000276:immunology; D000818:Animals; D000830:Animals, Laboratory / Q000276:immunology*; D004731:Endotoxins / Q000276:immunology; D005260:Female; D005838:Genotype; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics* / Q000276:immunology*; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D051197:Toll-Like Receptor 4 / Q000235:genetics* / Q000276:immunology*; D055815:Young Adult
D000485:Allergens; D004731:Endotoxins; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4