Occupational exposure to gases/fumes and mineral dust affect DNA methylation levels of genes regulating expression
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
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.
Date Issued
2019-08-01
Date Acceptance
2019-03-23
Citation
Human Molecular Genetics, 2019, 28 (15), pp.2477-2485
ISSN
0964-6906
Publisher
Oxford University Press (OUP)
Start Page
2477
End Page
2485
Journal / Book Title
Human Molecular Genetics
Volume
28
Issue
15
Copyright Statement
© 2019 The Authors. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/),
which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Subjects
Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Genetics & Heredity
DECLINE
DISCOVERY
GASES
RISK
FEV1
BIOS Consortium
Genetics & Heredity
06 Biological Sciences
11 Medical and Health Sciences
Publication Status
Published
Date Publish Online
2019-04-02