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

BACKGROUND: The biological mechanisms by which cleaning products and disinfectants - an emerging risk factor - affect respiratory health remain incompletely evaluated. Studying genes by environment interactions (GxE) may help identify new genes related to adult-onset asthma. OBJECTIVES: To identify...

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Autores: Rava, Marta, Ahmed, Ismail, Kogevinas, Manolis, Le Moual, Nicole, Bouzigon, Emmanuelle, Curjuric, Ivan, Dizier, Marie-Hélène, Dumas, Orianne, González, Juan Ramón, Imboden, Medea, Mehta, Amar J., Tubert-Bitter, Pascale, Zock, Jan-Paul, Jarvis, Deborah, Probst-Hensch, Nicole M., Demenais, Florence, Nadif, Rachel
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2016
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/101566
Acceso en línea:https://hdl.handle.net/2445/101566
Access Level:acceso abierto
Palabra clave:Malalties de l'aparell respiratori
Asma
Respiratory organs diseases
Asthma
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spelling Genes Interacting with Occupational Exposures to Low Molecular Weight Agents and Irritants on Adult-Onset Asthma in Three European StudiesRava, MartaAhmed, IsmailKogevinas, ManolisLe Moual, NicoleBouzigon, EmmanuelleCurjuric, IvanDizier, Marie-HélèneDumas, OrianneGonzález, Juan RamónImboden, MedeaMehta, Amar J.Tubert-Bitter, PascaleZock, Jan-PaulJarvis, DeborahProbst-Hensch, Nicole M.Demenais, FlorenceNadif, RachelMalalties de l'aparell respiratoriAsmaRespiratory organs diseasesAsthmaBACKGROUND: The biological mechanisms by which cleaning products and disinfectants - an emerging risk factor - affect respiratory health remain incompletely evaluated. Studying genes by environment interactions (GxE) may help identify new genes related to adult-onset asthma. OBJECTIVES: To identify 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. METHODS: Data came from three large European cohorts: EGEA, SAPALDIA, and ECRHS. A candidate pathway-based strategy identified 163 genes involved in response to oxidative stress and potentially related with 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 GxE interactions, adjusted for age, sex and population ancestry in 2599 adults (Mean age: 47 years, 60% women, 36% exposed, 18% asthmatics). P-values were corrected for multiple comparisons. RESULTS: Ever exposure to LMW agents/irritants was associated with current adult-onset asthma (OR(95%CI)=1.28(1.04,1.58)). Eight 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. CONCLUSIONS: Using a pathway-based selection process, we identified novel genes potentially involved in the adult asthma in relation with occupational exposure. These genes play a role in the NF-kB pathway involved in inflammation.National Institute of Environmental Health Sciences2016info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfhttps://hdl.handle.net/2445/101566Articles publicats en revistes (ISGlobal)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésVersió postprint del document publicat a: http://dx.doi.org/10.1289/EHP376Environmental Health Perspectives, 2016http://dx.doi.org/10.1289/EHP376Domini públic / Public domainhttp://creativecommons.org/publicdomain/mark/1.0/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1015662026-05-27T06:46:51Z
dc.title.none.fl_str_mv Genes Interacting with Occupational Exposures to Low Molecular Weight Agents and Irritants on Adult-Onset Asthma in Three European Studies
title Genes Interacting with Occupational Exposures to Low Molecular Weight Agents and Irritants on Adult-Onset Asthma in Three European Studies
spellingShingle Genes Interacting with Occupational Exposures to Low Molecular Weight Agents and Irritants on Adult-Onset Asthma in Three European Studies
Rava, Marta
Malalties de l'aparell respiratori
Asma
Respiratory organs diseases
Asthma
title_short Genes Interacting with Occupational Exposures to Low Molecular Weight Agents and Irritants on Adult-Onset Asthma in Three European Studies
title_full Genes Interacting with Occupational Exposures to Low Molecular Weight Agents and Irritants on Adult-Onset Asthma in Three European Studies
title_fullStr Genes Interacting with Occupational Exposures to Low Molecular Weight Agents and Irritants on Adult-Onset Asthma in Three European Studies
title_full_unstemmed Genes Interacting with Occupational Exposures to Low Molecular Weight Agents and Irritants on Adult-Onset Asthma in Three European Studies
title_sort Genes Interacting with Occupational Exposures to Low Molecular Weight Agents and Irritants on Adult-Onset Asthma in Three European Studies
dc.creator.none.fl_str_mv Rava, Marta
Ahmed, Ismail
Kogevinas, Manolis
Le Moual, Nicole
Bouzigon, Emmanuelle
Curjuric, Ivan
Dizier, Marie-Hélène
Dumas, Orianne
González, Juan Ramón
Imboden, Medea
Mehta, Amar J.
Tubert-Bitter, Pascale
Zock, Jan-Paul
Jarvis, Deborah
Probst-Hensch, Nicole M.
Demenais, Florence
Nadif, Rachel
author Rava, Marta
author_facet Rava, Marta
Ahmed, Ismail
Kogevinas, Manolis
Le Moual, Nicole
Bouzigon, Emmanuelle
Curjuric, Ivan
Dizier, Marie-Hélène
Dumas, Orianne
González, Juan Ramón
Imboden, Medea
Mehta, Amar J.
Tubert-Bitter, Pascale
Zock, Jan-Paul
Jarvis, Deborah
Probst-Hensch, Nicole M.
Demenais, Florence
Nadif, Rachel
author_role author
author2 Ahmed, Ismail
Kogevinas, Manolis
Le Moual, Nicole
Bouzigon, Emmanuelle
Curjuric, Ivan
Dizier, Marie-Hélène
Dumas, Orianne
González, Juan Ramón
Imboden, Medea
Mehta, Amar J.
Tubert-Bitter, Pascale
Zock, Jan-Paul
Jarvis, Deborah
Probst-Hensch, Nicole M.
Demenais, Florence
Nadif, Rachel
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Malalties de l'aparell respiratori
Asma
Respiratory organs diseases
Asthma
topic Malalties de l'aparell respiratori
Asma
Respiratory organs diseases
Asthma
description BACKGROUND: The biological mechanisms by which cleaning products and disinfectants - an emerging risk factor - affect respiratory health remain incompletely evaluated. Studying genes by environment interactions (GxE) may help identify new genes related to adult-onset asthma. OBJECTIVES: To identify 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. METHODS: Data came from three large European cohorts: EGEA, SAPALDIA, and ECRHS. A candidate pathway-based strategy identified 163 genes involved in response to oxidative stress and potentially related with 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 GxE interactions, adjusted for age, sex and population ancestry in 2599 adults (Mean age: 47 years, 60% women, 36% exposed, 18% asthmatics). P-values were corrected for multiple comparisons. RESULTS: Ever exposure to LMW agents/irritants was associated with current adult-onset asthma (OR(95%CI)=1.28(1.04,1.58)). Eight 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. CONCLUSIONS: Using a pathway-based selection process, we identified novel genes potentially involved in the adult asthma in relation with occupational exposure. These genes play a role in the NF-kB pathway involved in inflammation.
publishDate 2016
dc.date.none.fl_str_mv 2016
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/101566
url https://hdl.handle.net/2445/101566
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Versió postprint del document publicat a: http://dx.doi.org/10.1289/EHP376
Environmental Health Perspectives, 2016
http://dx.doi.org/10.1289/EHP376
dc.rights.none.fl_str_mv Domini públic / Public domain
http://creativecommons.org/publicdomain/mark/1.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Domini públic / Public domain
http://creativecommons.org/publicdomain/mark/1.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv National Institute of Environmental Health Sciences
publisher.none.fl_str_mv National Institute of Environmental Health Sciences
dc.source.none.fl_str_mv Articles publicats en revistes (ISGlobal)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,301603

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