Changes in DNA methylation after corticosteroids treatment in COPD patients

Introduction: Inhaled corticosteroids (ICS) are used to reduce inflammation in COPD and have shown to reduce the decline of FEV1 in a subset of COPD patients, but its effects on the methylome remain unknown. Aims: This project aims to investigate the effects of ICS on the methylation of CpG sites in COPD patients. Methods: Bronchial biopsies of COPD patients were obtained at baseline, 6 months, and 30 months post-ICS treatment and analyzed for changes in DNA methylation (Infinium Human Methylation 850k Bead Chip) and mRNA expression (RNA Seq, Illumina-NovaSeq6000 sequencing). We used a linear model (while correcting for age, gender, and smoking status, Limma v3.40.6) to identify changes in DNA methylation after treatment with ICS. Furthermore, we used eQTM analysis (MatrixEQTL v2.2) to identify which genes are possibly affected by these DNA methylation changes and subsequent pathway analysis (gProfiler) to identify genes and pathways affected by the designated methylation sites. Results: We found 990 significantly (Bonferroni FDR <0.05) altered CpG sites when comparing 6 months ICS treatment with baseline, of which 197 showed increased methylation, and 793 decreased. We found 680 cis-eQTM within 1Mbp of genes affected by the identified methylation sites. Furthermore, we showed that methylation sites correlate to gene expression after treatment with ICS. Genes negatively correlated to the identified methylation sites are predicted to be involved in inflammation. Conclusion: Six months of treatment of COPD patients with ICS alters CpG site methylation. Further analysis is needed to examine in what way ICS induced CpG site methylation regulates gene expression and pathways regulated to inflammation.