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Epigenetics and pulmonary diseases in the horizon of precision medicine: a review

Giuditta Benincasa, Dawn L. DeMeo, Kimberly Glass, Edwin K. Silverman, Claudio Napoli
European Respiratory Journal 2020; DOI: 10.1183/13993003.03406-2020
Giuditta Benincasa
1Department of Advanced Medical and Surgical Sciences (DAMSS), University of Campania “Luigi Vanvitelli”, Naples, Italy
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Dawn L. DeMeo
2Channing Division of Network Medicine and the Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
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Kimberly Glass
2Channing Division of Network Medicine and the Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
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Edwin K. Silverman
2Channing Division of Network Medicine and the Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
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Claudio Napoli
1Department of Advanced Medical and Surgical Sciences (DAMSS), University of Campania “Luigi Vanvitelli”, Naples, Italy
3Clinical Department of Internal and Specialty Medicine (DAI), University Hospital (AOU), University of Campania “Luigi Vanvitelli”, Naples, Italy
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Abstract

Epigenetic mechanisms represent potential molecular routes which could bridge the gap between genetic background and environmental risk factors contributing to the pathogenesis of pulmonary diseases. In patients with chronic obstructive pulmonary disease (COPD), asthma, and pulmonary arterial hypertension (PAH), there is emerging evidence of aberrant epigenetic marks, mainly including DNA methylation and histone modifications which directly mediate reversible modifications to the DNA without affecting the genomic sequence. Post-translational events and microRNAs can be also epigenetically regulated and potentially participate to disease pathogenesis. Thus, novel pathogenic mechanisms and putative biomarkers may be detectable in peripheral blood, sputum, nasal and buccal swabs, or lung tissue. Besides, DNA methylation plays an important role during the early phases of fetal development and may be impacted by environmental exposures, ultimately influencing an individual's susceptibility to COPD, asthma, and PAH later in life. With the advances in omics platforms and the application of computational biology tools, modelling the epigenetic variability in a network framework, rather than as single molecular defects, is providing insights into the possible molecular pathways underlying the pathogenesis of COPD, asthma, and PAH. Epigenetic modifications may have clinical applications as non-invasive biomarkers of pulmonary diseases. Moreover, combining molecular assays with network analysis of epigenomic data may aid in clarifying the multi-stage transition from a “pre-disease” to “disease” state, with the goal of improving primary prevention of lung diseases and its subsequent clinical management.

We describe epigenetic mechanisms known to be associated with pulmonary diseases and discuss how network analysis could improve our understanding of lung diseases.

Footnotes

This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.

Conflict of interest: Dr. Matson has nothing to disclose.

Conflict of interest: Dr. Benincasa has nothing to disclose.

Conflict of interest: Dr. DeMeo has nothing to disclose.

Conflict of interest: Dr. Glass has nothing to disclose.

Conflict of interest: Dr. Silverman has nothing to disclose.

Conflict of interest: Dr. Napoli has nothing to disclose.

  • Received September 6, 2020.
  • Accepted November 10, 2020.
  • Copyright ©ERS 2020
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Epigenetics and pulmonary diseases in the horizon of precision medicine: a review
Giuditta Benincasa, Dawn L. DeMeo, Kimberly Glass, Edwin K. Silverman, Claudio Napoli
European Respiratory Journal Jan 2020, 2003406; DOI: 10.1183/13993003.03406-2020

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Epigenetics and pulmonary diseases in the horizon of precision medicine: a review
Giuditta Benincasa, Dawn L. DeMeo, Kimberly Glass, Edwin K. Silverman, Claudio Napoli
European Respiratory Journal Jan 2020, 2003406; DOI: 10.1183/13993003.03406-2020
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