Occupational exposure to gases/fumes and mineral dust affect DNA methylation levels of genes regulating expression

Many workers are daily exposed to occupational agents like gases/fumes, mineral dust or biological dust, which could induce adverse health effects. Epigenetic mechanisms, such as DNA methylation, have been suggested to play a role. We therefore aimed to identify differentially methylated regions (DM...

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Main Authors: van der Plaat, DA, Vonk, JM, Terzikhan, N, de Jong, K, de Vries, M, La Bastide-van Gemert, S, van Diemen, CC, Lahousse, L, Brusselle, GG, Nedeljkovic, I, Amin, N, BIOS Consortium, Kromhout, H, Vermeulen, RCH, Postma, DS, van Duijn, CM, Boezen, HM
Format: Journal article
Language:English
Published: Oxford University Press 2019
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author van der Plaat, DA
Vonk, JM
Terzikhan, N
de Jong, K
de Vries, M
La Bastide-van Gemert, S
van Diemen, CC
Lahousse, L
Brusselle, GG
Nedeljkovic, I
Amin, N
BIOS Consortium
Kromhout, H
Vermeulen, RCH
Postma, DS
van Duijn, CM
Boezen, HM
author_facet van der Plaat, DA
Vonk, JM
Terzikhan, N
de Jong, K
de Vries, M
La Bastide-van Gemert, S
van Diemen, CC
Lahousse, L
Brusselle, GG
Nedeljkovic, I
Amin, N
BIOS Consortium
Kromhout, H
Vermeulen, RCH
Postma, DS
van Duijn, CM
Boezen, HM
author_sort van der Plaat, DA
collection OXFORD
description Many workers are daily exposed to occupational agents like gases/fumes, mineral dust or biological dust, which could induce adverse health effects. Epigenetic mechanisms, such as DNA methylation, have been suggested to play a role. We therefore aimed to identify differentially methylated regions (DMRs) upon occupational exposures in never-smokers and investigated if these DMRs associated with gene expression levels. To determine the effects of occupational exposures independent of smoking, 903 never-smokers of the LifeLines cohort study were included. We performed three genome-wide methylation analyses (Illumina 450 K), one per occupational exposure being gases/fumes, mineral dust and biological dust, using robust linear regression adjusted for appropriate confounders. DMRs were identified using comb-p in Python. Results were validated in the Rotterdam Study (233 never-smokers) and methylation-expression associations were assessed using Biobank-based Integrative Omics Study data (n = 2802). Of the total 21 significant DMRs, 14 DMRs were associated with gases/fumes and 7 with mineral dust. Three of these DMRs were associated with both exposures (RPLP1 and LINC02169 (2×)) and 11 DMRs were located within transcript start sites of gene expression regulating genes. We replicated two DMRs with gases/fumes (VTRNA2-1 and GNAS) and one with mineral dust (CCDC144NL). In addition, nine gases/fumes DMRs and six mineral dust DMRs significantly associated with gene expression levels. Our data suggest that occupational exposures may induce differential methylation of gene expression regulating genes and thereby may induce adverse health effects. Given the millions of workers that are exposed daily to occupational exposures, further studies on this epigenetic mechanism and health outcomes are warranted.
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spelling oxford-uuid:e2d75e71-48e1-44fd-8767-e672fcef07222022-03-27T10:04:30ZOccupational exposure to gases/fumes and mineral dust affect DNA methylation levels of genes regulating expressionJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:e2d75e71-48e1-44fd-8767-e672fcef0722EnglishSymplectic ElementsOxford University Press2019van der Plaat, DAVonk, JMTerzikhan, Nde Jong, Kde Vries, MLa Bastide-van Gemert, Svan Diemen, CCLahousse, LBrusselle, GGNedeljkovic, IAmin, NBIOS ConsortiumKromhout, HVermeulen, RCHPostma, DSvan Duijn, CMBoezen, HMMany workers are daily exposed to occupational agents like gases/fumes, mineral dust or biological dust, which could induce adverse health effects. Epigenetic mechanisms, such as DNA methylation, have been suggested to play a role. We therefore aimed to identify differentially methylated regions (DMRs) upon occupational exposures in never-smokers and investigated if these DMRs associated with gene expression levels. To determine the effects of occupational exposures independent of smoking, 903 never-smokers of the LifeLines cohort study were included. We performed three genome-wide methylation analyses (Illumina 450 K), one per occupational exposure being gases/fumes, mineral dust and biological dust, using robust linear regression adjusted for appropriate confounders. DMRs were identified using comb-p in Python. Results were validated in the Rotterdam Study (233 never-smokers) and methylation-expression associations were assessed using Biobank-based Integrative Omics Study data (n = 2802). Of the total 21 significant DMRs, 14 DMRs were associated with gases/fumes and 7 with mineral dust. Three of these DMRs were associated with both exposures (RPLP1 and LINC02169 (2×)) and 11 DMRs were located within transcript start sites of gene expression regulating genes. We replicated two DMRs with gases/fumes (VTRNA2-1 and GNAS) and one with mineral dust (CCDC144NL). In addition, nine gases/fumes DMRs and six mineral dust DMRs significantly associated with gene expression levels. Our data suggest that occupational exposures may induce differential methylation of gene expression regulating genes and thereby may induce adverse health effects. Given the millions of workers that are exposed daily to occupational exposures, further studies on this epigenetic mechanism and health outcomes are warranted.
spellingShingle van der Plaat, DA
Vonk, JM
Terzikhan, N
de Jong, K
de Vries, M
La Bastide-van Gemert, S
van Diemen, CC
Lahousse, L
Brusselle, GG
Nedeljkovic, I
Amin, N
BIOS Consortium
Kromhout, H
Vermeulen, RCH
Postma, DS
van Duijn, CM
Boezen, HM
Occupational exposure to gases/fumes and mineral dust affect DNA methylation levels of genes regulating expression
title Occupational exposure to gases/fumes and mineral dust affect DNA methylation levels of genes regulating expression
title_full Occupational exposure to gases/fumes and mineral dust affect DNA methylation levels of genes regulating expression
title_fullStr Occupational exposure to gases/fumes and mineral dust affect DNA methylation levels of genes regulating expression
title_full_unstemmed Occupational exposure to gases/fumes and mineral dust affect DNA methylation levels of genes regulating expression
title_short Occupational exposure to gases/fumes and mineral dust affect DNA methylation levels of genes regulating expression
title_sort occupational exposure to gases fumes and mineral dust affect dna methylation levels of genes regulating expression
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