• Ana I Hernández Cordero, Chen Xi Yang, Julia Yang, Steve Horvath, Tawimas Shaipanich, Julia MacIsaac, David T S Lin, Michael S Kobor, Silvia Guillemi, Marianne Harris, Wan Lam, Stephen Lam, Julio Montaner, ManS F PaulSFPCentre for Heart Lung Innovation, St. Paul's Hospital and University of British Columbia, Vancouver, British Columbia, Canada.Division of Respiratory Medicine, Department of Medicine., Don D Sin, and Janice M Leung.
• Centre for Heart Lung Innovation, St. Paul's Hospital and University of British Columbia, Vancouver, British Columbia, Canada.
• Am. J. Respir. Crit. Care Med. 2022 Jul 15; 206 (2): 150160150-160.

AbstractRationale: 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. Objectives: To identify whether accelerated aging can be observed in the airways of PLWH with COPD, manifest by a unique DNA methylation signature. Methods: Bronchial epithelial brushings from PLWH with and without COPD and HIV-uninfected adults with and without COPD (N = 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. Measurements and Main Results: 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 (ABLIM3) was one of the novel candidate genes for HIV-associated COPD highlighted by our analysis. Conclusions: 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.

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