title: Gene-environment interactions influence airways function in laboratory animal workers.
abstract: BACKGROUND
  Most diseases, including asthma, result from the interaction between environmental exposures and genetic variants. Functional variants of CD14 negatively affect lung function in farm workers and children exposed to animal allergens and endotoxin.
  
  
  OBJECTIVE
  We hypothesized that CD14 polymorphisms interact with inhaled endotoxin, mouse allergen, or both to decrease airways function in laboratory animal workers.
  
  
  METHODS
  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.
  
  
  RESULTS
  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 FEV(1) and forced expiratory flow, midexpiratory phase (FEF(25-75)) 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.
  
  
  CONCLUSIONS
  A significant gene-environment interaction affects airways function in laboratory animal workers. More highly endotoxin-exposed workers with CD14/-1619G alleles have significantly lower FEV(1) and FEF(25-75) percent predicted than those with CD14/-1619AA alleles. Atopic workers are particularly affected by cumulative endotoxin exposures.
authors.affiliation: Department of Medicine, Division of Environmental and Occupational Health Sciences, National Jewish Health, Denver, CO 80206, USA. pachecok@njhealth.org
authors.forename: Karin A
authors.initials: KA
authors.lastname: Pacheco
authors.forename: Cecile S
authors.initials: CS
authors.lastname: Rose
authors.forename: Lori J
authors.initials: LJ
authors.lastname: Silveira
authors.forename: Michael V
authors.initials: MV
authors.lastname: Van Dyke
authors.forename: Kelly
authors.initials: K
authors.lastname: Goelz
authors.forename: Kristyn
authors.initials: K
authors.lastname: MacPhail
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Maier
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000395:Air Pollutants, Occupational / Q000009:adverse effects*; D000483:Alleles; D000485:Allergens / Q000009:adverse effects*; D000818:Animals; D001249:Asthma / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D004731:Endotoxins / Q000009:adverse effects*; D005540:Forced Expiratory Flow Rates; D005838:Genotype; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000235:genetics*; D008297:Male; D017056:Medical Laboratory Personnel; D051379:Mice; D008875:Middle Aged; D016273:Occupational Exposure / Q000009:adverse effects*; D011110:Polymorphism, Genetic
chemical_list: D000395:Air Pollutants, Occupational; D000485:Allergens; D004731:Endotoxins; D018950:Lipopolysaccharide Receptors