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© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Epigenetic modifications are common in chronic obstructive pulmonary disease (COPD); however, their clinical relevance is largely unknown. We hypothesized that epigenetic disruptions are associated with symptoms and health status in COPD. We profiled the blood (n = 57) and airways (n = 62) of COPD patients for DNA methylation (n = 55 paired). The patients’ health status was assessed using the St. George’s Respiratory Questionnaire (SGRQ). We conducted differential methylation analyses and identified pathways characterized by epigenetic disruptions associated with SGRQ scores and its individual domains. 29,211 and 5044 differentially methylated positions (DMPs) were associated with total SGRQ scores in blood and airway samples, respectively. The activity, impact, and symptom domains were associated with 9161, 25,689 and 17,293 DMPs in blood, respectively; and 4674, 3730 and 5063 DMPs in airways, respectively. There was a substantial overlap of DMPs between airway and blood. DMPs were enriched for pathways related to common co-morbidities of COPD (e.g., ageing, cancer and neurological) in both tissues. Health status in COPD is associated with airway and systemic epigenetic changes especially in pathways related to co-morbidities of COPD. There are more blood DMPs than in the airways suggesting that blood epigenome is a promising source to discover biomarkers for clinical outcomes in COPD.

Details

Title
Systemic and Airway Epigenetic Disruptions Are Associated with Health Status in COPD
Author
Hernandez Cordero, Ana I 1 ; Li, Xuan 2 ; Chen Xi Yang 2 ; Yang, Julia 3 ; MacIsaac, Julia L 4 ; Dever, Kristy 4 ; Kobor, Michael S 4 ; Milne, Stephen 5   VIAFID ORCID Logo  ; van Eeden, Stephan F 3   VIAFID ORCID Logo  ; Shaipanich, Tawimas 6 ; Lam, Stephen 7 ; Leung, Janice M 8 ; Sin, Don D 8   VIAFID ORCID Logo 

 Centre for Heart Lung Innovation, St. Paul’s Hospital and University of British Columbia, Vancouver, BC V6Z 1Y6, Canada; Edwin S.H. Leong Healthy Aging Program, Department of Medical Genetics, University of British Columbia, Vancouver, BC V6T 1Z3, Canada 
 Centre for Heart Lung Innovation, St. Paul’s Hospital and University of British Columbia, Vancouver, BC V6Z 1Y6, Canada 
 Centre for Heart Lung Innovation, St. Paul’s Hospital and University of British Columbia, Vancouver, BC V6Z 1Y6, Canada; Division of Respiratory Medicine, Department of Medicine, University of British Columbia, Vancouver, BC V5Z 1M9, Canada 
 Edwin S.H. Leong Healthy Aging Program, Department of Medical Genetics, University of British Columbia, Vancouver, BC V6T 1Z3, Canada 
 Centre for Heart Lung Innovation, St. Paul’s Hospital and University of British Columbia, Vancouver, BC V6Z 1Y6, Canada; Division of Respiratory Medicine, Department of Medicine, University of British Columbia, Vancouver, BC V5Z 1M9, Canada; Sydney Medical School, The University of Sydney, Sydney, NSW 2050, Australia 
 Division of Respiratory Medicine, Department of Medicine, University of British Columbia, Vancouver, BC V5Z 1M9, Canada 
 Centre for Heart Lung Innovation, St. Paul’s Hospital and University of British Columbia, Vancouver, BC V6Z 1Y6, Canada; Division of Respiratory Medicine, Department of Medicine, University of British Columbia, Vancouver, BC V5Z 1M9, Canada; British Columbia Cancer Agency, Vancouver, BC V5Z 1G1, Canada 
 Centre for Heart Lung Innovation, St. Paul’s Hospital and University of British Columbia, Vancouver, BC V6Z 1Y6, Canada; Edwin S.H. Leong Healthy Aging Program, Department of Medical Genetics, University of British Columbia, Vancouver, BC V6T 1Z3, Canada; Division of Respiratory Medicine, Department of Medicine, University of British Columbia, Vancouver, BC V5Z 1M9, Canada 
First page
134
Publication year
2023
Publication date
2023
Publisher
MDPI AG
e-ISSN
22279059
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2767181507
Copyright
© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.