We hypothesized that CD14 polymorphisms interact with inhaled endotoxin, mouse allergen, or both to decrease airways function in laboratory animal workers.
Three hundred sixty-nine Caucasian workers completed a symptom and work exposure questionnaire, skin prick testing, and spirometry. Individual exposure estimates for endotoxin and murine allergen were calculated by weighting task-based breathing zone concentrations by time reported for each task and length of time in the current job. Real-time PCR was used to assess CD14/−1619, −550, and −159 alleles. Multiple linear regression predicting airways function included an interaction term between genotype and exposure.
Workers at the highest quartile of the natural log-transformed cumulative endotoxin exposure and with the endotoxin-responsive CD14/−1619 G allele had significantly lower FEV1 and forced expiratory flow, midexpiratory phase (FEF25-75) percent predicted compared with workers with an AA genotype, with no significant differences noted at lower endotoxin levels for either genotype. The gene-environment effect was marked for atopic workers. Laboratory animal allergy, murine allergen exposure, CD14/−159 or −550 genotype, and a gene-exposure interaction term for these genotypes and exposures did not predict changes in lung function.
A significant gene-environment interaction affects airways function in laboratory animal workers. More highly endotoxin-exposed workers with CD14/−1619G alleles have significantly lower FEV1 and FEF25-75 percent predicted than those with CD14/−1619AA alleles. Atopic workers are particularly affected by cumulative endotoxin exposures.