Genes Interacting with Occupational Exposures to Low Molecular Weight Agents and Irritants on Adult-Onset Asthma in Three European Studies

• Marta Rava ^[3] ; Ismail Ahmed ^[4] ; Manolis Kogevinas ^[5] ; Nicole Le Moual ^[6] ; Emmanuelle Bouzigon ^[7] ; Ivan Curjuric ^[8] ; Marie-Hélène Dizier ^[7] ; Orianne Dumas ^[6] ; Juan R. Gonzalez ^[5] ; Medea Imboden ^[8] ; Amar J. Mehta ^[1] ; Pascale Tubert-Bitter ^[4] ; Jan-Paul Zock ^[2] ; Deborah Jarvis ^[9] ; Nicole M. Probst-Hensch ^[8] ; Florence Demenais ^[7] ; Rachel Nadif ^[6]
  1. [1] Swiss Tropical and Public Health Institute

     Swiss Tropical and Public Health Institute

     Basilea, Suiza

     
  2. [2] Universitat Pompeu Fabra

     Universitat Pompeu Fabra

     Barcelona, España

     
  3. [3] 1 Inserm, U1168, VIMA: Aging and Chronic Diseases, Epidemiological and Public Health Approaches, Villejuif, France; 2 Spanish National Cancer Research Centre (CNIO), Genetic and Molecular Epidemiology Group, Human Cancer Genetics Program, Madrid, Spain
  4. [4] 3 Inserm UMR 1181 [Biostatistics, Biomathematics, Pharmacoepidemiology and Infectious Diseases (B2PHI)], Villejuif, France; 4 Institut Pasteur, UMR 1181, B2PHI, Paris, France; 5 Univ Versailles St.-Quentin-en-Yvelines, UMR 1181, B2PHI, Montigny le Bretonneux, France
  5. [5] 6 ISGlobal, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain; 7 CIBER Epidemiología y Salud Pública, Madrid, Spain
  6. [6] 1 Inserm, U1168, VIMA: Aging and Chronic Diseases, Epidemiological and Public Health Approaches, Villejuif, France; 8 Univ Versailles St.-Quentin-en-Yvelines, UMR-S 1168, Montigny le Bretonneux, France
  7. [7] 9 Inserm, UMR-946, Genetic Variation and Human Diseases Unit, Paris, France; 10 Univ Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d’Hématologie, Paris, France
  8. [8] 11 Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland; 12 University of Basel, Switzerland
  9. [9] 15 Respiratory Epidemiology and Public Health, Imperial College, London, United Kingdom; 16 MRC-HPA (Medical Research Council and Health Protection Agency) Centre for Environment and Health, London, United Kingdom

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• Localización: Environmental health perspectives, ISSN 0091-6765, Vol. 125, Nº. 2, 2017, págs. 207-214
• Idioma: inglés
• DOI: 10.1289/EHP376
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  • Texto completo
• Resumen

  • The biological mechanisms by which cleaning products and disinfectants—an emerging risk factor—affect respiratory health remain incompletely evaluated. Studying genes by environment interactions (G × E) may help identify new genes related to adult-onset asthma.

    We identified interactions between genetic polymorphisms of a large set of genes involved in the response to oxidative stress and occupational exposures to low molecular weight (LMW) agents or irritants on adult-onset asthma.

    Our data came from three large European cohorts: Epidemiological Family-based Study of the Genetics and Environment of Asthma (EGEA), Swiss Cohort Study on Air Pollution and Lung and Heart Disease in Adults (SAPALDIA), and European Community Respiratory Health Survey in Adults (ECRHS). A candidate pathway–based strategy identified 163 genes involved in the response to oxidative stress and potentially related to exposures to LMW agents/irritants. Occupational exposures were evaluated using an asthma job-exposure matrix and job-specific questionnaires for cleaners and healthcare workers. Logistic regression models were used to detect G × E interactions, adjusted for age, sex, and population ancestry, in 2,599 adults (mean age, 47 years; 60% women, 36% exposed, 18% asthmatics). p-Values were corrected for multiple comparisons.

    Ever exposure to LMW agents/irritants was associated with current adult-onset asthma [OR = 1.28 (95% CI: 1.04, 1.58)]. Eight single nucleotide polymorphism (SNP) by exposure interactions at five loci were found at p < 0.005: PLA2G4A (rs932476, chromosome 1), near PLA2R1 (rs2667026, chromosome 2), near RELA (rs931127, rs7949980, chromosome 11), PRKD1 (rs1958980, rs11847351, rs1958987, chromosome 14), and PRKCA (rs6504453, chromosome 17). Results were consistent across the three studies and after accounting for smoking.

    Using a pathway-based selection process, we identified novel genes potentially involved in adult asthma by interaction with occupational exposure. These genes play a role in the NF-κB pathway, which is involved in inflammation.

    Rava M, Ahmed I, Kogevinas M, Le Moual N, Bouzigon E, Curjuric I, Dizier MH, Dumas O, Gonzalez JR, Imboden M, Mehta AJ, Tubert-Bitter P, Zock JP, Jarvis D, Probst-Hensch NM, Demenais F, Nadif R. 2017. Genes interacting with occupational exposures to low molecular weight agents and irritants on adult-onset asthma in three European studies. Environ Health Perspect 125:207–214; http://dx.doi.org/10.1289/EHP376

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