Abstract
In 2023, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) introduced a provision regarding preserved ratio-impaired spirometry (PRISm), a presumed pre-stage of Chronic Obstructive Pulmonary Disease (COPD), into the COPD guidelines. However, further research in this area is needed. Our study aimed to investigate the epigenetic differences between PRISm and COPD. EWAS (n = 572) and RNA-sequencing (n = 60) were performed on blood samples from the COPD registry, and EWAS was replicated in the KoGES cohort data (n = 98). Our findings revealed significant epigenetic differences between patients with PRISm and COPD. 39,980 CpG-sites displayed differential methylation between PRISm and COPD. Seven gene regions-EEF1A2, EMP2, EPCAM, MTSS1L, ARHGEF10, HYDIN, and FADS2 were not only differentially methylated but also exhibited differential expression. The consistency of differential methylation of CpG sites in five genes, excluding ARHGEF10 and MTSS1L, was replicated in the KoGES study, affirming the distinction between COPD and PRISm. Our research identified seven gene regions as critical contributors related to the modulation of gene expression, including CpG sites that differentiate COPD from PRISm. These results highlight the significance of DNA methylation changes in distinguishing PRISm from COPD and shed light on potential mechanisms by which methylation alterations impact lung function.