Airway Aging and Methylation Disruptions in HIV-associated Chronic Obstructive Pulmonary Disease

Age-related diseases like chronic obstructive pulmonary disease (COPD) occur at higher rates in people living with human immunodeficiency virus (PLWH) than in uninfected populations. To identify whether accelerated aging can be observed in the airways of PLWH with COPD, manifest by a unique DNA meth...

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Bibliographic Details
Published in:American journal of respiratory and critical care medicine 2022-07, Vol.206 (2), p.150-160
Main Authors: Hernández Cordero, Ana I, Yang, Chen Xi, Yang, Julia, Horvath, Steve, Shaipanich, Tawimas, MacIsaac, Julia, Lin, David T S, Kobor, Michael S, Guillemi, Silvia, Harris, Marianne, Lam, Wan, Lam, Stephen, Montaner, Julio, Man, S F Paul, Sin, Don D, Leung, Janice M
Format: Article
Language:English
Subjects:
Adult
Aging - genetics
Chronic obstructive pulmonary disease
DNA methylation
DNA Methylation - genetics
Epigenomics
Gene expression
HIV
HIV Infections - complications
HIV Infections - genetics
Human immunodeficiency virus
Humans
Medical research
Original
Pulmonary Disease, Chronic Obstructive - complications
Pulmonary Disease, Chronic Obstructive - epidemiology
Pulmonary Disease, Chronic Obstructive - genetics
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Summary:Age-related diseases like chronic obstructive pulmonary disease (COPD) occur at higher rates in people living with human immunodeficiency virus (PLWH) than in uninfected populations. To identify whether accelerated aging can be observed in the airways of PLWH with COPD, manifest by a unique DNA methylation signature. Bronchial epithelial brushings from PLWH with and without COPD and HIV-uninfected adults with and without COPD (  = 76) were profiled for DNA methylation and gene expression. We evaluated global Alu and LINE-1 methylation and calculated the epigenetic age using the Horvath clock and the methylation telomere length estimator. To identify genome-wide differential DNA methylation and gene expression associated with HIV and COPD, robust linear models were used followed by an expression quantitative trait methylation (eQTM) analysis. Epigenetic age acceleration and shorter methylation estimates of telomere length were found in PLWH with COPD compared with PLWH without COPD and uninfected patients with and without COPD. Global hypomethylation was identified in PLWH. We identified 7,970 cytosine bases located next to a guanine base (CpG sites), 293 genes, and 9 expression quantitative trait methylation-gene pairs associated with the interaction between HIV and COPD. Actin binding LIM protein family member 3 ( ) was one of the novel candidate genes for HIV-associated COPD highlighted by our analysis. Methylation age acceleration is observed in the airway epithelium of PLWH with COPD, a process that may be responsible for the heightened risk of COPD in this population. Their distinct methylation profile, differing from that observed in patients with COPD alone, suggests a unique pathogenesis to HIV-associated COPD. The associations warrant further investigation to establish causality.
ISSN:1073-449X
1535-4970
DOI:10.1164/rccm.202106-1440OC