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Genes interacting with occupational exposures to low molecular weight agents and irritants on adult-onset asthma in three european studies

Rava, Marta and Ahmed, Ismail and Kogevinas, Manolis and Le Moual, Nicole and Bouzigon, Emmanuelle and Curjuric, Ivan and Dizier, Marie-Hélène and Dumas, Orianne and Gonzalez, Juan R. and Imboden, Medea and Mehta, Amar J. and Tubert-Bitter, Pascale and Zock, Jan-Paul and Jarvis, Deborah and Probst-Hensch, Nicole M. and Demenais, Florence and Nadif, Rachel. (2017) Genes interacting with occupational exposures to low molecular weight agents and irritants on adult-onset asthma in three european studies. Environmental Health Perspectives, 125 (2). pp. 207-214.

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Abstract

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. Citation: 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.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Epidemiology and Public Health (EPH) > Chronic Disease Epidemiology > Exposome Science (Probst-Hensch)
03 Faculty of Medicine > Departement Public Health > Sozial- und Präventivmedizin > Exposome Science (Probst-Hensch)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
UniBasel Contributors:Curjuric, Ivan and Imboden, Medea and Mehta, Amar and Probst Hensch, Nicole
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:National Institute of Environmental Health Sciences
ISSN:0091-6765
e-ISSN:1552-9924
Note:Publication type according to Uni Basel Research Database: Journal article -- Reproduced with permission from Environmental Health Perspectives
Language:English
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Last Modified:31 Aug 2017 07:49
Deposited On:24 Apr 2017 14:21

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