Promoting respiratory public health through epigenetics research: an ERS Environment Health Committee workshop report

Barouki, Robert; Barry, Maeve; Boezen, H. Marike; Hoffmann, Barbara; Krauss‐Etschmann, Susanne; Koppelman, Gerard H.; Forsberg, Bertil

doi:10.1183/13993003.02410-2017

Cited by 8 publications

(17 citation statements)

References 31 publications

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“…This interdisciplinary approach may provide an important method for future research in the clinical utility of epigenetic markers. Similar studies may also help evaluate differential methylation between different asthma phenotypes and determine the potential benefits of epigenetic variations in phenotyping patients with asthma for a more precise approach in treatment …”

Section: Discussionmentioning

confidence: 99%

Epigenome‐wide association studies in asthma: A systematic review

Edris

Dekker

Melén

et al. 2019

Clin Experimental Allergy

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Objective Asthma is a common chronic respiratory airway disease influenced by environmental factors and possibly their interaction with the human genome causing epigenetic changes. Epigenome‐wide association studies (EWAS) have mainly investigated DNA methylation and its association with disease or traits, exposure factors or gene expression. This systematic review aimed to identify all EWAS assessing differentially methylated sites associated with asthma in humans. Design Structured systematic literature search following PRISMA guidelines, Newcastle‐Ottawa Scale (NOS) for cohort studies was used for bias assessment. Data Sources We searched PubMed and Embase databases from 2005 to 2019. Eligibility Criteria Epigenome‐wide association studies testing association between differential methylation and asthma in humans. Results Overall, we identified 16 EWAS studies complying with our search criteria. Twelve studies were conducted on children, and 10 were conducted on sample sizes <150 subjects. Four hundred and nineteen CpGs were reported in children studies after correction for multiple testing. In the adult studies, thousands of differentially methylated sites were identified. Differential methylation in inflammatory‐related genes correlated with higher levels of gene expressions of inflammatory modulators in asthma. Differentially methylated genes associated with asthma included SMAD3, SERPINC1, PROK1, IL13, RUNX3 and TIGIT. Forty‐one CpGs were replicated at least once in blood samples, and 28 CpGs were replicated in nasal samples. Conclusion Although many differentially methylated CpGs in genes known to be involved in asthma have been identified in EWAS to date, we conclude that further studies of larger sample sizes and analyses of differential methylation between different phenotypes are needed in order to comprehensively evaluate the role of epigenetic factors in the pathophysiology and heterogeneity of asthma, and the potential clinical utility to predict or classify patients with asthma.

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Section: Discussionmentioning

confidence: 99%

Epigenome‐wide association studies in asthma: A systematic review

Edris

Dekker

Melén

et al. 2019

Clin Experimental Allergy

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“…More recently, a study of five European birth cohorts (n = 10 860) showed that maternal smoking during infancy correlated with a 15% (95%CI: 0%‐31%) increase in the risk of asthma in children . Interestingly, SHS exposure might induce epigenetic changes with transgenerational repercussions on asthma onset, which would imply a very long‐term effect of tobacco smoking on respiratory health. The immaturity of the immune and respiratory systems of children and their larger air volume per weight kilogram inhaled as compared to adults might explain the high sensitivity to tobacco smoke during childhood .…”

Section: Indoor Air Pollutionmentioning

confidence: 99%

“…An early analysis of the ESCAPE project did not find a statistically significant association between air pollution and the development of asthma up to the school age 73. However, the re-analysis of these cohorts when the study individuals were 14-16 years old revealed associations between asthma incidence and NO 2 (OR 1.13, 95% CI: 1.02-1 25). and PM 2.5 (OR 1.29, 95% CI: 1.00-1.66) exposure.…”

mentioning

confidence: 95%

The need for clean air: The way air pollution and climate change affect allergic rhinitis and asthma

Eguiluz‐Gracia

Mathioudakis

Bartel

et al. 2020

Allergy

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311

193

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Air pollution and climate change have a significant impact on human health and well‐being and contribute to the onset and aggravation of allergic rhinitis and asthma among other chronic respiratory diseases. In Westernized countries, households have experienced a process of increasing insulation and individuals tend to spend most of their time indoors. These sequelae implicate a high exposure to indoor allergens (house dust mites, pets, molds, etc), tobacco smoke, and other pollutants, which have an impact on respiratory health. Outdoor air pollution derived from traffic and other human activities not only has a direct negative effect on human health but also enhances the allergenicity of some plants and contributes to global warming. Climate change modifies the availability and distribution of plant‐ and fungal‐derived allergens and increases the frequency of extreme climate events. This review summarizes the effects of indoor air pollution, outdoor air pollution, and subsequent climate change on asthma and allergic rhinitis in children and adults and addresses the policy adjustments and lifestyle changes required to mitigate their deleterious effects.

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“…Even though occupational exposures are common, it is still largely unknown how these exposures are involved in (lung) disease development. Epigenetic mechanisms such as DNA methylation have been suggested to play a role, and researchers have therefore advocated the importance of epigenetic studies into environmental exposures and lung health (7). Environmental exposures, like occupational exposures, induce changes in DNA methylation levels, which can affect gene expression, possibly aiding in disease development (8).…”

Section: Introductionmentioning

confidence: 99%

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

Plaat

Vonk

Terzikhan

et al. 2019

Human Molecular Genetics

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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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Promoting respiratory public health through epigenetics research: an ERS Environment Health Committee workshop report

Cited by 8 publications

References 31 publications

Epigenome‐wide association studies in asthma: A systematic review

Epigenome‐wide association studies in asthma: A systematic review

The need for clean air: The way air pollution and climate change affect allergic rhinitis and asthma

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

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