DNA methylation is associated with airflow obstruction in patients living with HIV

Ana I. Hernandez Cordero, Chen Xi Yang, Maen Obeidat, Julia Yang, Julie Macisaac, Lisa McEwen, David Lin, Michael Kobor, Richard Novak, Fleur Hudson, Hartwig Klinker, Nila Dharan, Sf Paul Man, Don D. Sin, Ken Kunisaki, Janice Leung

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

INTRODUCTION: People living with HIV (PLWH) suffer from age-related comorbidities such as COPD. The processes responsible for reduced lung function in PLWH are largely unknown. We performed an epigenome-wide association study to investigate whether blood DNA methylation is associated with impaired lung function in PLWH.

METHODS: Using blood DNA methylation profiles from 161 PLWH, we tested the effect of methylation on FEV 1, FEV 1/FVC ratio and FEV 1 decline over a median of 5 years. We evaluated the global methylation of PLWH with airflow obstruction by testing the differential methylation of transposable elements Alu and LINE-1, a well-described marker of epigenetic ageing.

RESULTS: Airflow obstruction as defined by a FEV 1/FVC<0.70 was associated with 1393 differentially methylated positions (DMPs), while 4676 were associated with airflow obstruction based on the FEV 1/FVC<lower limit of normal. These DMPs were enriched for biological pathways associated with chronic viral infections. The airflow obstruction group was globally hypomethylated compared with those without airflow obstruction. 103 and 7112 DMPs were associated with FEV 1 and FEV 1/FVC, respectively. No positions were associated with FEV 1 decline.

CONCLUSION: A large number of DMPs were associated with airflow obstruction and lung function in a unique cohort of PLWH. Airflow obstruction in even relatively young PLWH is associated with global hypomethylation, suggesting advanced epigenetic ageing compared with those with normal lung function. The disturbance of the epigenetic regulation of key genes not previously identified in non-HIV COPD cohorts could explain the unique risk of COPD in PLWH.

Original languageEnglish (US)
Pages (from-to)448-455
Number of pages8
JournalThorax
Volume76
Issue number5
Early online dateDec 18 2020
DOIs
StatePublished - May 1 2021

Bibliographical note

Funding Information:
Funding AIHC is supported by MITACS accelerate. This study was supported by the Canadian Institutes of Health Research (F15-00958). JML is supported by the Michael Smith Foundation for Health Research and the Canadian Institutes of Health Research. The START Pulmonary Substudy was supported by the National Heart Lung and Blood Institute [R01 HL096453]; the parent START trial was primarily supported by the National Institute of Allergy and Infectious Diseases Division of AIDS [UM1 AI068641 and UM AI120197] with additional support from the German Ministry of Education and Research, the European AIDS Treatment Network (NEAT), the Australian National Health and Medical Research Council, and the UK Medical Research Council and National Institute for Health Research. The Veterans Health Administration Office of Research and Development also provided protected research time in support of this study. The University of Minnesota served as sponsor of the study.

Publisher Copyright:
© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Keywords

  • COPD ÀÜ mechanisms
  • immunodeficiency
  • respiratory measurement
  • viral infection

PubMed: MeSH publication types

  • Journal Article
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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