Genetic predictors of inflammation in the risk of occupational asthma in young apprentices |
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| Authors: | Dovi Stéphanie Acouetey Denis Zmirou-Navier Patrice Avogbe Paul Tossa Thomas Rémen Annick Barbaud José-Antonio Cornejo-Garcia Miguel Blanca Abraham Bohadana Christophe Paris Jean-Louis Guéant Rosa-Maria Guéant-Rodriguez |
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| Affiliation: | 1. Nutrition, Genetics and Environment, INSERM-U954, Faculty of Medecine, Vandoeuvre lès Nancy, France;2. Ecole des Hautes Etudes en Santé Publique, Rennes, France;3. Research Laboratory, Carlos Haya Hospital-Fundacion IMABIS, Malaga, Spain;1. Division of Allergy and Immunology, Children''s Memorial Hospital, and the Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, Ill;2. Department of Medicine, University of California, San Francisco, Calif;3. Department of Genetics, Stanford University School of Medicine, Stanford, Calif;4. Department of Biological Systems, Division of Biological and Health Sciences, Universidad Autónoma Metropolitana-Xochimilco, Mexico City, Mexico;5. Division of Allergy-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, Ill;6. Department of Pediatrics, Section of Pulmonology, Baylor College of Medicine, Texas Children''s Hospital, Houston, Tex;7. Allergy/Immunology Associates and the Departments of Medicine and Pediatrics, Case Western Reserve University, Cleveland, Ohio;8. Veterans Caribbean Health Care System, San Juan, Puerto Rico;9. Centro de Neumologia Pediatrica, CSP, San Juan, Puerto Rico;10. Pediatric Pulmonary Division, Jacobi Medical Center, Bronx, NY;11. Department of Pediatrics, University of California, San Francisco, Calif;12. Department of Internal Medicine, Henry Ford Health System, Detroit, Mich;13. Basic Research Laboratory, SAIC-Frederick, Center for Cancer Research, National Cancer Institute, Frederick, Md;14. Department of Health Sciences, Graduate Program in Public Health, Lehman College, City University of New York, Bronx, NY;15. Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, Calif;1. Department of Microbiology and Immunology, Cornell University, Ithaca, NY;3. Baker Institute for Animal Health, Department of Biomedical Sciences, Cornell University, Ithaca, NY;2. Department of Veterinary and Biomedical Sciences, Pennsylvania State University, University Park, Pa;3. From King''s College London and the Medical Research Council and Asthma UK Centre in Allergic Mechanisms of Asthma, Randall Division of Cell and Molecular Biophysics, Guy''s Campus, London, SE1 1UL and;4. the Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, United Kingdom;1. Christian Doppler Laboratory for Allergy Research, Medical University of Vienna, Vienna, Austria;2. Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria;3. Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria;4. Institute of Molecular Biosciences, University of Graz, Graz, Austria |
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| Abstract: | BackgroundThe influence of genetic predictors of inflammation and atopy on occupational asthma in apprentices is not known.ObjectivesTo 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.MethodsA 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.ResultsIL13 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).ConclusionWe 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. |
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