EBioMedicine (Sep 2022)
The relationship between the epigenetic aging biomarker “grimage” and lung function in both the airway and blood of people living with HIV: An observational cohort study
- Ana I Hernández Cordero,
- Chen Xi Yang,
- Julia Yang,
- Xuan Li,
- Steve Horvath,
- Tawimas Shaipanich,
- Julia MacIsaac,
- David Lin,
- Lisa McEwen,
- Michael S. Kobor,
- Silvia Guillemi,
- Marianne Harris,
- Wan Lam,
- Stephen Lam,
- Ma'en Obeidat,
- Richard M. Novak,
- Fleur Hudson,
- Hartwig Klinker,
- Nila Dharan,
- Julio Montaner,
- S.F. Paul Man,
- Ken Kunisaki,
- Don D. Sin,
- Janice M. Leung,
- J.V. Baker,
- D. Duprez,
- A. Carr,
- J. Hoy,
- M. Dolan,
- A. Telenti,
- C. Grady,
- G. Matthews,
- J. Rockstroh,
- W.H. Belloso,
- J.M. Kagan,
- E. Wright,
- B. Brew,
- R.W. Price,
- K. Robertson,
- L. Cysique,
- K.M. Kunisaki,
- J.E. Connett,
- D.E. Niewoehner,
- Endpoint Review Committee,
- A. Lifson,
- W.H. Belloso,
- R.T. Davey, Jr.,
- D. Duprez,
- J.M. Gatell,
- J. Hoy,
- C. Pedersen,
- R.W. Price,
- R. Prineas,
- J. Worley
Affiliations
- Ana I Hernández Cordero
- Centre for Heart Lung Innovation, St. Paul's Hospital and University of British Columbia, Vancouver, British Columbia, Canada
- Chen Xi Yang
- Centre for Heart Lung Innovation, St. Paul's Hospital and University of British Columbia, Vancouver, British Columbia, Canada
- Julia Yang
- Centre for Heart Lung Innovation, St. Paul's Hospital and University of British Columbia, Vancouver, British Columbia, Canada
- Xuan Li
- Centre for Heart Lung Innovation, St. Paul's Hospital and University of British Columbia, Vancouver, British Columbia, Canada
- Steve Horvath
- Department of Biostatistics, Fielding School of Public Health, University of California Los Angeles (UCLA), Los Angeles, CA 90095, United States; Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles (UCLA), Los Angeles, CA 90095, United States
- Tawimas Shaipanich
- Division of Respiratory Medicine, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
- Julia MacIsaac
- Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada
- David Lin
- Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada
- Lisa McEwen
- Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada
- Michael S. Kobor
- Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada
- Silvia Guillemi
- British Columbia Centre for Excellence in HIV/AIDS, Providence Health Care, Vancouver, British Columbia, Canada; Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
- Marianne Harris
- British Columbia Centre for Excellence in HIV/AIDS, Providence Health Care, Vancouver, British Columbia, Canada; Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
- Wan Lam
- British Columbia Cancer Research Centre and the University of British Columbia, Vancouver, British Columbia
- Stephen Lam
- British Columbia Cancer Research Centre and the University of British Columbia, Vancouver, British Columbia
- Ma'en Obeidat
- Centre for Heart Lung Innovation, St. Paul's Hospital and University of British Columbia, Vancouver, British Columbia, Canada
- Richard M. Novak
- Section of Infectious Diseases, University of Illinois at Chicago, Chicago, IL, United States
- Fleur Hudson
- MRC Clinical Trials Unit, University College London, London, UK
- Hartwig Klinker
- Medizinische Klinik und Poliklinik II, Universitatsklinikum Wurzburg, Wurzburg, Germany
- Nila Dharan
- The Kirby Institute, UNSW Sydney, Sydney, New South Wales, Australia
- Julio Montaner
- British Columbia Centre for Excellence in HIV/AIDS, Providence Health Care, Vancouver, British Columbia, Canada; Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
- S.F. Paul Man
- Centre for Heart Lung Innovation, St. Paul's Hospital and University of British Columbia, Vancouver, British Columbia, Canada; Division of Respiratory Medicine, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
- Ken Kunisaki
- Minneapolis Veterans Affairs Health Care System, Section of Pulmonary, Critical Care and Sleep Medicine and the Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, University of Minnesota, Minneapolis, MN, United States
- Don D. Sin
- Centre for Heart Lung Innovation, St. Paul's Hospital and University of British Columbia, Vancouver, British Columbia, Canada; Division of Respiratory Medicine, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
- Janice M. Leung
- Centre for Heart Lung Innovation, St. Paul's Hospital and University of British Columbia, Vancouver, British Columbia, Canada; Division of Respiratory Medicine, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada; Corresponding author at: Room 166-1081 Burrard St, Centre for Heart Lung Innovation, Vancouver, BC V6Z 1Y6.
- J.V. Baker
- D. Duprez
- A. Carr
- J. Hoy
- M. Dolan
- A. Telenti
- C. Grady
- G. Matthews
- J. Rockstroh
- W.H. Belloso
- J.M. Kagan
- E. Wright
- B. Brew
- R.W. Price
- K. Robertson
- L. Cysique
- K.M. Kunisaki
- J.E. Connett
- D.E. Niewoehner
- Endpoint Review Committee
- A. Lifson
- W.H. Belloso
- R.T. Davey, Jr.
- D. Duprez
- J.M. Gatell
- J. Hoy
- C. Pedersen
- R.W. Price
- R. Prineas
- J. Worley
- Journal volume & issue
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Vol. 83
p. 104206
Abstract
Summary: Background: Age-related comorbidities such as chronic obstructive pulmonary disease (COPD) are common in people living with human immunodeficiency virus (PLWH). We investigated the relationship between COPD and the epigenetic age of the airway epithelium and peripheral blood of PLWH. Methods: Airway epithelial brushings from 34 PLWH enrolled in the St. Paul's Hospital HIV Bronchoscopy cohort and peripheral blood from 378 PLWH enrolled in The Strategic Timing of Antiretroviral Treatment (START) study were profiled for DNA methylation. The DNA methylation biomarker of age and healthspan, GrimAge, was calculated in both tissue compartments. We tested the association of GrimAge with COPD in the airway epithelium and airflow obstruction as defined by an FEV1/FVC<0.70, and FEV1 decline over 6 years in blood. Findings: The airway epithelium of PLWH with COPD was associated with greater GrimAge residuals compared to PLWH without COPD (Beta=3.18, 95%CI=1.06-5.31, P=0.005). In blood, FEV1/FVC<LLN was associated with greater GrimAge residuals (Beta=1.74, 95%CI=0.37-3.24, P=0.019). FEV1 decline was inversely correlated with GrimAge residuals in blood (r=−0.13, P=0.012). PLWH who had normal lung function but who subsequently developed an FEV1/FVC<0.70 over the course of 6 years had higher GrimAge residuals at baseline (Beta=2.33, 95%CI=0.23-4.44, P=0.031). Interpretation: GrimAge may reflect lung and systemic epigenetic changes that occur with advanced airflow obstruction and may help to identify PLWH with a higher risk of developing COPD. Funding: Canadian Institutes of Health Research and the British Columbia Lung Association. The START substudy was funded by NIH grants: UM1-AI068641, UM1-AI120197, and RO1HL096453.
