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Epigenetic marker of telomeric age is associated with exacerbations and hospitalizations in chronic obstructive pulmonary disease
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...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8693486/ https://www.ncbi.nlm.nih.gov/pubmed/34937547 http://dx.doi.org/10.1186/s12931-021-01911-9 |
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author | 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. Paul Leung, Janice M. Sin, Don D. |
author_facet | 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. Paul Leung, Janice M. Sin, Don D. |
author_sort | Hernández Cordero, Ana I. |
collection | PubMed |
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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12931-021-01911-9. |
format | Online Article Text |
id | pubmed-8693486 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-86934862021-12-23 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. Paul Leung, Janice M. Sin, Don D. Respir Res Research 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12931-021-01911-9. BioMed Central 2021-12-22 2021 /pmc/articles/PMC8693486/ /pubmed/34937547 http://dx.doi.org/10.1186/s12931-021-01911-9 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research 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. Paul Leung, Janice M. Sin, Don D. Epigenetic marker of telomeric age is associated with exacerbations and hospitalizations in chronic obstructive pulmonary disease |
title | Epigenetic marker of telomeric age is associated with exacerbations and hospitalizations in chronic obstructive pulmonary disease |
title_full | Epigenetic marker of telomeric age is associated with exacerbations and hospitalizations in chronic obstructive pulmonary disease |
title_fullStr | Epigenetic marker of telomeric age is associated with exacerbations and hospitalizations in chronic obstructive pulmonary disease |
title_full_unstemmed | Epigenetic marker of telomeric age is associated with exacerbations and hospitalizations in chronic obstructive pulmonary disease |
title_short | Epigenetic marker of telomeric age is associated with exacerbations and hospitalizations in chronic obstructive pulmonary disease |
title_sort | epigenetic marker of telomeric age is associated with exacerbations and hospitalizations in chronic obstructive pulmonary disease |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8693486/ https://www.ncbi.nlm.nih.gov/pubmed/34937547 http://dx.doi.org/10.1186/s12931-021-01911-9 |
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