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Epigenetic marker of telomeric age is associated with exacerbations and hospitalizations in chronic obstructive pulmonary disease Hernández Cordero, Ana I.; Yang, Chen Xi; Li, Xuan; Milne, Stephen; Chen, Virginia; Hollander, Zsuzsanna; Ng, Raymond; Criner, Gerard J.; Woodruff, Prescott G.; Lazarus, Stephen C.; Connett, John E.; Han, MeiLan K.; Martinez, Fernando J.; Reed, Robert M.; Man, S. F. P.; Leung, Janice M.; Sin, Don D.

Abstract

Background Chronic obstructive pulmonary disease (COPD) is an age-related condition that has been associated with early telomere attrition; the clinical implications of telomere shortening in COPD are not well known. In this study we aimed to determine the relationship of the epigenetic regulation of telomeric length in peripheral blood with the risk of exacerbations and hospitalization in patients with COPD. Methods Blood DNA methylation profiles were obtained from 292 patients with COPD enrolled in the placebo arm of the Macrolide Azithromycin to Prevent Rapid Worsening of Symptoms Associated with Chronic Obstructive Pulmonary Disease (MACRO) Study and who were followed for 1-year. We calculated telomere length based on DNA methylation markers (DNAmTL) and related this biomarker to the risk of exacerbation and hospitalization and health status (St. George Respiratory Questionnaire [SGRQ]) score over time using a Cox proportional hazards model. We also used linear models to investigate the associations of DNAmTL with the rates of exacerbation and hospitalization (adjusted for chronological age, lung function, race, sex, smoking, body mass index and cell composition). Results Participants with short DNAmTL demonstrated increased risk of exacerbation (P = 0.02) and hospitalization (P = 0.03) compared to those with longer DNAmTL. DNAmTL age acceleration was associated with higher rates of exacerbation (P = 1.35 × 10–04) and hospitalization (P = 5.21 × 10–03) and poor health status (lower SGRQ scores) independent of chronological age (P = 0.03). Conclusion Telomeric age based on blood DNA methylation is associated with COPD exacerbation and hospitalization and thus a promising biomarker for poor outcomes in COPD.

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Title
Epigenetic marker of telomeric age is associated with exacerbations and hospitalizations in chronic obstructive pulmonary disease
Creator
Hernández Cordero, Ana I.; Yang, Chen Xi; Li, Xuan; Milne, Stephen; Chen, Virginia; Hollander, Zsuzsanna; Ng, Raymond; Criner, Gerard J.; Woodruff, Prescott G.; Lazarus, Stephen C.; Connett, John E.; Han, MeiLan K.; Martinez, Fernando J.; Reed, Robert M.; Man, S. F. P.; Leung, Janice M.; Sin, Don D.
Contributor
University of British Columbia. Centre for Heart Lung Innovation; St. Paul's Hospital (Vancouver, B.C.)
Publisher
BioMed Central
Date Issued
2021-12-22
Description
Background Chronic obstructive pulmonary disease (COPD) is an age-related condition that has been associated with early telomere attrition; the clinical implications of telomere shortening in COPD are not well known. In this study we aimed to determine the relationship of the epigenetic regulation of telomeric length in peripheral blood with the risk of exacerbations and hospitalization in patients with COPD. Methods Blood DNA methylation profiles were obtained from 292 patients with COPD enrolled in the placebo arm of the Macrolide Azithromycin to Prevent Rapid Worsening of Symptoms Associated with Chronic Obstructive Pulmonary Disease (MACRO) Study and who were followed for 1-year. We calculated telomere length based on DNA methylation markers (DNAmTL) and related this biomarker to the risk of exacerbation and hospitalization and health status (St. George Respiratory Questionnaire [SGRQ]) score over time using a Cox proportional hazards model. We also used linear models to investigate the associations of DNAmTL with the rates of exacerbation and hospitalization (adjusted for chronological age, lung function, race, sex, smoking, body mass index and cell composition). Results Participants with short DNAmTL demonstrated increased risk of exacerbation (P = 0.02) and hospitalization (P = 0.03) compared to those with longer DNAmTL. DNAmTL age acceleration was associated with higher rates of exacerbation (P = 1.35 × 10–04) and hospitalization (P = 5.21 × 10–03) and poor health status (lower SGRQ scores) independent of chronological age (P = 0.03). Conclusion Telomeric age based on blood DNA methylation is associated with COPD exacerbation and hospitalization and thus a promising biomarker for poor outcomes in COPD.
Subject
COPD; Telomeres; AECOPD; Epigenetics; DNA methylation
Genre
Article
Type
Text
Language
eng
Date Available
2022-01-25
Provider
Vancouver : University of British Columbia Library
Rights
Attribution 4.0 International (CC BY 4.0)
DOI
10.14288/1.0406345
URI
http://hdl.handle.net/2429/80725
Affiliation
Medicine, Faculty of; Non UBC; Medicine, Department of
Citation
Respiratory Research. 2021 Dec 22;22(1):316
Publisher DOI
10.1186/s12931-021-01911-9
Peer Review Status
Reviewed
Scholarly Level
Faculty; Researcher; Other
Copyright Holder
The Author(s)
Rights URI
http://creativecommons.org/licenses/by/4.0/
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Attribution 4.0 International (CC BY 4.0)