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Genomics ; 111(6): 1381-1386, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-30248490

RESUMO

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.


Assuntos
Corticosteroides/uso terapêutico , Metilação de DNA , Epigênese Genética , Marcadores Genéticos , Doença Pulmonar Obstrutiva Crônica/genética , Ventilação Pulmonar/genética , Insuficiência Respiratória/genética , Estudos de Casos e Controles , Genoma Humano , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Fenótipo , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/patologia , Ventilação Pulmonar/efeitos dos fármacos , Insuficiência Respiratória/tratamento farmacológico , Insuficiência Respiratória/patologia
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