Choi Eun-A, Kim Hyun Jeong, Kim Youlim, Jang Han Byul, Hwang Yong Il, Kim Young-Youl, Yoo Kwang Ha, Lee Hye-Ja
Division of Allergy and Respiratory Disease Research, Department of Chronic Disease Convergence Research, Korea National Institute of Health, Korea Disease Control and Prevention Agency, Osong-Eup, Heungdeok-Gu, Cheongju, Republic of Korea.
Division of Pulmonary and Allergy Medicine, Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Republic of Korea.
Funct Integr Genomics. 2025 Apr 10;25(1):86. doi: 10.1007/s10142-025-01593-2.
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.
2023年，慢性阻塞性肺疾病全球倡议组织（GOLD）在慢性阻塞性肺疾病（COPD）指南中引入了关于保留比率受损肺量计（PRISm，一种推测的COPD前期阶段）的条款。然而，该领域还需要进一步研究。我们的研究旨在调查PRISm与COPD之间的表观遗传学差异。对来自COPD登记处的血样进行了全基因组甲基化分析（EWAS，n = 572）和RNA测序（n = 60），并在韩国基因组与流行病学研究（KoGES）队列数据（n = 98）中重复了EWAS。我们的研究结果揭示了PRISm患者与COPD患者之间存在显著的表观遗传学差异。39980个CpG位点在PRISm和COPD之间表现出甲基化差异。七个基因区域——EEF1A2、EMP2、EPCAM、MTSS1L、ARHGEF10、HYDIN和FADS2不仅存在甲基化差异，而且表现出表达差异。在KoGES研究中重复了五个基因（不包括ARHGEF10和MTSS1L）中CpG位点甲基化差异的一致性，证实了COPD和PRISm之间的区别。我们的研究确定了七个基因区域是与基因表达调控相关的关键因素，包括区分COPD和PRISm的CpG位点。这些结果突出了DNA甲基化变化在区分PRISm和COPD中的重要性，并揭示了甲基化改变影响肺功能的潜在机制。
