title: Genetic predictors of inflammation in the risk of occupational asthma in young apprentices.
abstract: BACKGROUND
  The influence of genetic predictors of inflammation and atopy on occupational asthma in apprentices is not known.
  
  
  OBJECTIVE
  To assess the influence of genetic polymorphisms of IL4RA, IL13, TNFA, IL1A, and IL5 on the decline of lung function and bronchial hyperresponsiveness in a prospective follow-up study of baker/pastry maker and hairdresser apprentices.
  
  
  METHODS
  A total of 351 apprentices were included in the study. We performed skin testing, spirometry, fractional exhaled nitric oxide measurement, and methacholine hyperreactivity testing at the initial visit and during and at the end of the 18-month training period. Gene variants of IL4RA, IL13, TNFA, IL1A, and IL5 were determined in DNA from nasal lavage.
  
  
  RESULTS
  IL13 R130Q/IL4RA S478P or IL13 R130Q//IL4RA Q551R were significant predictors of the decrease of forced expiratory volume and forced vital capacity (P ≤ .006). Genotype GG of TNFAG308A was associated with bronchial hyperresponsiveness in the whole population and in nonatopic individuals (90.63% vs 9.38%; odds ratio, 3.78; 95% confidence interval, 1.10-12.83). TNFA GA and IL5 CC and TNFA GA and IL1A CC were 2 epistatic predictors of exhaled nitrogen monoxide decrease during follow-up (P = .02 and P = .004, respectively). The association with TNFA GA and IL1A CC was the most significant in nonatopic bakers (P < .001).
  
  
  CONCLUSIONS
  We evidenced a predicting influence of IL13/IL4RA and TNFA in the early exposure to allergens and irritants that precedes occupational asthma. The significance of the associations in the absence of atopy suggests an influence of the genetics predictors related to inflammatory pathways.
authors.affiliation: Nutrition, Genetics and Environment, INSERM-U954, Faculty of Medecine, Vandoeuvre lès Nancy, France.
authors.forename: Dovi Stéphanie
authors.initials: DS
authors.lastname: Acouetey
authors.forename: Denis
authors.initials: D
authors.lastname: Zmirou-Navier
authors.forename: Patrice Hodonou
authors.initials: PH
authors.lastname: Avogbe
authors.forename: Patrice
authors.initials: P
authors.lastname: Avogbe
authors.forename: Paul
authors.initials: P
authors.lastname: Tossa
authors.forename: Thomas
authors.initials: T
authors.lastname: Rémen
authors.forename: Annick
authors.initials: A
authors.lastname: Barbaud
authors.forename: José-Antonio
authors.initials: JA
authors.lastname: Cornejo-Garcia
authors.forename: Miguel
authors.initials: M
authors.lastname: Blanca
authors.forename: Abraham
authors.initials: A
authors.lastname: Bohadana
authors.forename: Christophe
authors.initials: C
authors.lastname: Paris
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Guéant
authors.forename: Rosa-Maria
authors.initials: RM
authors.lastname: Guéant-Rodriguez
mesh_terms: D000293:Adolescent; D000402:Airway Obstruction / Q000235:genetics / Q000503:physiopathology; D059366:Asthma, Occupational / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D016535:Bronchial Hyperreactivity / Q000235:genetics / Q000503:physiopathology; D045853:Exhalation; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D015994:Incidence; D007249:Inflammation / Q000235:genetics*; D018793:Interleukin-13 / Q000235:genetics; D008297:Male; D009569:Nitric Oxide / Q000032:analysis; D016273:Occupational Exposure; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D019948:Receptors, Interleukin-4 / Q000235:genetics; D012306:Risk; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D018793:Interleukin-13; D019948:Receptors, Interleukin-4; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide