DNA Methylation Is Globally Disrupted and Associated with Expression Changes in Chronic Obstructive Pulmonary Disease Small Airways

Vucic, Emily A.; Chari, Raj; Thu, Kelsie L.; Wilson, Ian M.; Cotton, Allison M.; Kennett, Jennifer Y.; Zhang, May; Lonergan, Kim M.; Steiling, Katrina; Brown, Carolyn J.; McWilliams, Annette; Ohtani, Keishi; Lenburg, Marc E.; Sin, Don D.; Spira, Avrum; MacAulay, Calum; Lam, Stephen; Lam, Wan L.

doi:10.1165/rcmb.2013-0304oc

Cited by 125 publications

(117 citation statements)

References 70 publications

(81 reference statements)

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“…quantitative lung function and cumulative smoker exposure (47). Functional annotation clustering revealed a significant enrichment of several domains.…”

Section: Original Researchmentioning

confidence: 98%

Smoking-Associated Site-Specific Differential Methylation in Buccal Mucosa in the COPDGene Study

Wan

Qiu

Carey

et al. 2015

Am J Respir Cell Mol Biol

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DNA methylation is a complex, tissue-specific phenomenon that can reflect both endogenous factors and exogenous exposures. Buccal brushings represent an easily accessible source of DNA, which may be an appropriate surrogate tissue in the study of environmental exposures and chronic respiratory diseases. Buccal brushings were obtained from a subset of current and former smokers from the COPDGene study. Genome-wide DNA methylation data were obtained in the discovery cohort (n = 82) using the Illumina HumanMethylation450K array. Empirical Bayes methods were used to test for differential methylation by current smoking status at 468,219 autosomal CpG sites using linear models adjusted for age, sex, and race. Pyrosequencing was performed in a nonoverlapping replication cohort (n = 130). Current smokers were significantly younger than former smokers in both the discovery and replication cohorts. Seven CpG sites were associated with current smoking at a false discovery rate less than 0.05 in the discovery cohort. Six of the seven significant sites were pyrosequenced in the replication cohort; five CpG sites, including sites annotated to CYP1B1 and PARVA, were replicated. Correlations between cumulative smoke exposure and time since smoking cessation were observed in a subset of the significantly associated CpG sites. A significant correlation between reduced lung function and increased radiographic emphysema with methylation at cg02162897 (CYP1B1) was observed among female subjects. Site-specific methylation of DNA isolated from buccal mucosa is associated with exposure to cigarette smoke, and may provide insights into the mechanisms underlying differential susceptibility toward the development of smoking-related chronic respiratory diseases.

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“…quantitative lung function and cumulative smoker exposure (47). Functional annotation clustering revealed a significant enrichment of several domains.…”

Section: Original Researchmentioning

confidence: 98%

Smoking-Associated Site-Specific Differential Methylation in Buccal Mucosa in the COPDGene Study

Wan

Qiu

Carey

et al. 2015

Am J Respir Cell Mol Biol

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“…Circumstantial evidence indicates a role for altered DNA methylation in the pathogenesis of COPD; both, cigarette and wood smoke induce changes in DNA methylation that have been associated with an increased risk for development of COPD [58,59]. A globally altered DNA methylation pattern has only recently been described in small airway epithelial cells [60]. Differential DNA methylation was also detected in lymphocytes of COPD patients compared to healthy controls and correlated with altered lung function and COPD severity [61].…”

Section: Epigenetic Alterationsmentioning

confidence: 99%

Hallmarks of the ageing lung

2015

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Ageing is the main risk factor for major non-communicable chronic lung diseases, including chronic obstructive pulmonary disease, most forms of lung cancer and idiopathic pulmonary fibrosis. While the prevalence of these diseases continually increases with age, their respective incidence peaks at different times during the lifespan, suggesting specific effects of ageing on the onset and/or pathogenesis of chronic obstructive pulmonary disease, lung cancer and idiopathic pulmonary fibrosis. Recently, the nine hallmarks of ageing have been defined as cell-autonomous and non-autonomous pathways involved in ageing. Here, we review the available evidence for the involvement of each of these hallmarks in the pathogenesis of chronic obstructive pulmonary disease, lung cancer, or idiopathic pulmonary fibrosis. Importantly, we propose an additional hallmark, "dysregulation of the extracellular matrix", which we argue acts as a crucial modifier of cell-autonomous changes and functions, and as a key feature of the above-mentioned lung diseases. @ERSpublications Hallmarks of ageing are selecting factors for the pathogenesis of COPD, lung cancer and IPF

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“…As such, micronuclei formation is associated with a high risk of cancer and is a common assay that is used to screen for genotoxic substances, and increased micronuclei formation has been observed in cigarette smokers (43,149). Tobacco smoke has also been shown to alter gene expression and DNA methylation in both the whole lung and in airway epithelia (69,115,153), macrophages (47), and endothelia (161). Many of these assays have been established as outcome measures for tobacco smoke exposure, and they should be useful for probing the effects of E-Cig exposure.…”

Section: Effects Of E-cig Aerosols and E-liquids On Cultured Cells Frmentioning

confidence: 99%

Will chronic e-cigarette use cause lung disease?

Rowell

Tarran

2015

American Journal of Physiology-Lung Cellular and Molecular Phys

102

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Chronic tobacco smoking is a major cause of preventable morbidity and mortality worldwide. In the lung, tobacco smoking increases the risk of lung cancer, and also causes chronic obstructive pulmonary disease (COPD), which encompasses both emphysema and chronic bronchitis. E-cigarettes (E-Cigs), or electronic nicotine delivery systems, were developed over a decade ago and are designed to deliver nicotine without combusting tobacco. Although tobacco smoking has declined since the 1950s, E-Cig usage has increased, attracting both former tobacco smokers and never smokers. E-Cig liquids (e-liquids) contain nicotine in a glycerol/propylene glycol vehicle with flavorings, which are vaporized and inhaled. To date, neither E-Cig devices, nor e-liquids, are regulated by the Food and Drug Administration (FDA). The FDA has proposed a deeming rule, which aims to initiate legislation to regulate E-Cigs, but the timeline to take effect is uncertain. Proponents of E-Cigs say that they are safe and should not be regulated. Opposition is varied, with some opponents proposing that E-Cig usage will introduce a new generation to nicotine addiction, reversing the decline seen with tobacco smoking, or that E-Cigs generally may not be safe and will trigger diseases like tobacco. In this review, we shall discuss what is known about the effects of E-Cigs on the mammalian lung and isolated lung cells in vitro. We hope that collating this data will help illustrate gaps in the knowledge of this burgeoning field, directing researchers toward answering whether or not E-Cigs are capable of causing disease.

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DNA Methylation Is Globally Disrupted and Associated with Expression Changes in Chronic Obstructive Pulmonary Disease Small Airways

Cited by 125 publications

References 70 publications

Smoking-Associated Site-Specific Differential Methylation in Buccal Mucosa in the COPDGene Study

Smoking-Associated Site-Specific Differential Methylation in Buccal Mucosa in the COPDGene Study

Hallmarks of the ageing lung

Will chronic e-cigarette use cause lung disease?

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