Epigenetic profiles integrated with transcriptomic reveal the difference between COPD and PRISm in KOCOSS-NIH.

Area of Science:

• Epigenetics
• Pulmonology
• Genomics

Background:

• The Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines now include preserved ratio-impaired spirometry (PRISm).
• PRISm is considered a potential precursor to Chronic Obstructive Pulmonary Disease (COPD).
• Further research is needed to understand the relationship and distinctions between PRISm and COPD.

Purpose of the Study:

• To investigate the epigenetic differences between PRISm and COPD.
• To identify specific DNA methylation patterns that differentiate PRISm from COPD.

Main Methods:

• Epigenome-wide association studies (EWAS) were conducted on blood samples from 572 individuals in the COPD registry.
• RNA sequencing was performed on 60 samples.
• EWAS findings were replicated in the KoGES cohort (n=98).

Main Results:

• Significant epigenetic differences were observed between PRISm and COPD patients.
• 39,980 CpG sites showed differential methylation between the two groups.
• Seven gene regions (EEF1A2, EMP2, EPCAM, MTSS1L, ARHGEF10, HYDIN, FADS2) exhibited both differential methylation and expression, with five showing consistent replication in the KoGES study.

Conclusions:

• DNA methylation patterns significantly distinguish PRISm from COPD.
• Seven identified gene regions are critical in modulating gene expression and differentiating these conditions.
• These findings provide insights into the role of epigenetic alterations in lung function decline and the progression from PRISm to COPD.