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Genetic susceptibility to laboratory animal allergy

Posted on:2000-02-24Degree:Ph.DType:Dissertation
University:The Johns Hopkins UniversityCandidate:Wiesch, Denise GFull Text:PDF
GTID:1464390014463078Subject:Health Sciences
Abstract/Summary:
Laboratory animal allergy (LAA), the common term used in the literature to describe allergy that results from occupational exposure to experimental animals, is a major cause of disability among exposed persons. This study was designed to determine why certain individuals are susceptible to developing LAA while others remain unaffected. The primary goal was to identify genetic susceptibility to LAA in terms of polymorphisms in two candidate genes, the IL-4 and the IL-4 receptor (IL-4r).;Employees at The Jackson Laboratory, a mouse research and breeding facility Bar Harbor, Maine, were studied utilizing a two-stage design. The first stage, a cross-sectional study of the entire population of 881 persons, was implemented primarily to identify cases and controls and optimize their numbers for the subsequent association study. Five hundred five employees responded to the survey; LAA prevalence and exposure-disease relationships were determined. Ninety-one workers with LAA symptoms were frequency matched by exposure and gender to 101 persons without symptoms for the subsequent case-control study. Data collection from these individuals included a questionnaire, 18 skintests, spirometry, and blood withdrawal for DNA isolation and serum IgE analyses. Forty-six cases were ultimately narrowed to include persons having both LAA symptoms and sensitization to mice. Eighty-five controls had no LAA symptoms and no evidence of mouse sensitization.;LAA prevalence was 35%. Self-reported exposure to mice was strongly associated to LAA symptoms and showed a dose-response relationship (e.g. OR = 1.0, 7.4, 30.0 for low, medium, and high cumulative time exposure respectively). Atopy, but not smoking, was associated with LAA symptoms and sensitization (OR = 10.9). There was no evidence for LAA association with polymorphisms in the IL-4 or IL-4 receptor. Marginally significant associations with total IgE (p = 0.05) and mouse specific IgE (p = 0.02) were seen for IL-4(-590) and IL-4r(576) respectively.;We conclude that although only 51% of individuals with LAA symptoms appear to be sensitized, LAA is a major heath concern at The Jackson Laboratory. Atopic individuals may be at greater risk for LAA and should be targeted for preventive strategies. We found no convincing evidence for susceptibility to LAA or atopy based on IL-4 or IL-4r polymorphisms.
Keywords/Search Tags:LAA, IL-4, Susceptibility, Laboratory, Exposure
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