Epigenetic marker of telomeric age is associated with exacerbations and hospitalizations in chronic obstructive pulmonary disease

Respiratory Research

Chen Xi Yang¹  Xuan Li¹  Ana I. Hernández Cordero¹  Janice M. Leung²  Don D. Sin²  S. F. Paul Man²  Stephen Milne³  Zsuzsanna Hollander⁴  MeiLan K. Han⁵  Prescott G. Woodruff⁶  Stephen C. Lazarus⁶  Gerard J. Criner⁷  Robert M. Reed⁸  Fernando J. Martinez⁹  Raymond Ng^1,10  Virginia Chen^1,10  John E. Connett^1,11 

[1] Centre for Heart Lung Innovation, St. Paul’s Hospital and University of British Columbia, Room 166-1081 Burrard St, V6Z 1Y6, Vancouver, BC, Canada;Centre for Heart Lung Innovation, St. Paul’s Hospital and University of British Columbia, Room 166-1081 Burrard St, V6Z 1Y6, Vancouver, BC, Canada;Division of Respiratory Medicine, Department of Medicine, University of British Columbia, Vancouver, BC, Canada;Centre for Heart Lung Innovation, St. Paul’s Hospital and University of British Columbia, Room 166-1081 Burrard St, V6Z 1Y6, Vancouver, BC, Canada;Division of Respiratory Medicine, Department of Medicine, University of British Columbia, Vancouver, BC, Canada;Sydney Medical School, Faculty of Medicine and Health Sciences, University of Sydney, Sydney, NSW, Australia;Centre for Heart Lung Innovation, St. Paul’s Hospital and University of British Columbia, Room 166-1081 Burrard St, V6Z 1Y6, Vancouver, BC, Canada;PROOF Centre of Excellence, St. Paul’s Hospital, Vancouver, BC, Canada;Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA;Department of Medicine, University of California San Francisco, San Francisco, CA, USA;Department of Thoracic Medicine and Surgery, Temple University, Philadelphia, PA, USA;Division of Pulmonary and Critical Care Medicine, University of Maryland School of Medicine, Baltimore, MD, USA;Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medical College, Cornell University, New York, NY, USA;PROOF Centre of Excellence, St. Paul’s Hospital, Vancouver, BC, Canada;School of Public Health, University of Minnesota, Minneapolis, MN, USA;

关键词: COPD;    Telomeres;    AECOPD;    Epigenetics;    DNA methylation;   

DOI  :  10.1186/s12931-021-01911-9

来源: Springer

【 摘 要 】

BackgroundChronic 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.MethodsBlood 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).ResultsParticipants 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).ConclusionTelomeric age based on blood DNA methylation is associated with COPD exacerbation and hospitalization and thus a promising biomarker for poor outcomes in COPD.

【 授权许可】

CC BY