Identifying heterogeneity in chronic obstructive pulmonary disease (COPD) phenotypes is important for the development of personalized medicine. Genome-wide analysis was used to compare the methylation levels of peripheral blood mononuclear cell (PBMC) samples from 24 acute-exacerbation (AE) COPD patients with good/poor response to corticosteroid therapy and 12 non-COPD controls. Pyrosequencing was employed to validate the genome-wide analysis. In the dataset specific to COPD patients with a good response, enrichment was identified for the following: genes in the Ubl conjugation pathway, nicotinamide nucleotide metabolism, the alkaloid metabolic process, and regulation of the glucose metabolic process. Validation results confirmed CpG sites in PRKAG2 with different methylation levels in COPD patients and normal subjects. The CpG sites of ALOX5AP were specifically associated with a good response. The results suggested that a good response to corticosteroid treatment for AE-COPD should be considered a distinct subtype according to the putative epigenetic mechanism.
Adrenal Cortex Hormones/therapeutic use , DNA Methylation , Epigenesis, Genetic , Genetic Markers , Pulmonary Disease, Chronic Obstructive/genetics , Pulmonary Ventilation/genetics , Respiratory Insufficiency/genetics , Case-Control Studies , Genome, Human , Humans , Leukocytes, Mononuclear/drug effects , Leukocytes, Mononuclear/metabolism , Phenotype , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/pathology , Pulmonary Ventilation/drug effects , Respiratory Insufficiency/drug therapy , Respiratory Insufficiency/pathology
