Transcriptomics

Dataset Information

4

Methylation profiles of COPD small airways


ABSTRACT: Rationale: DNA methylation is an epigenetic modification that is highly disrupted in response to cigarette smoke and involved in a wide spectrum of malignant and non-malignant diseases, but surprisingly not previously assessed in small airways of patients with chronic obstructive pulmonary disease (COPD). Small airways are the primary sites of airflow obstruction in COPD. We sought to determine whether DNA methylation patterns are disrupted in small airway epithelia of COPD patients, and evaluate whether changes in gene expression are associated with these disruptions. Methods: Genome-wide methylation and gene expression analysis were performed on small airway epithelial DNA and RNA obtained from the same patient during bronchoscopy, using Illumina's Infinium HM27 and Affymetrix's Genechip Human Gene 1.0 ST arrays. To control for known effects of cigarette smoking on DNA methylation, methylation and gene expression profiles were compared between former smokers (FS) with and without COPD matched for age, pack years and years of smoking cessation. Results: Our results indicate that aberrant DNA methylation is i) a genome-wide phenomenon in small airways of patients with COPD and ii) associated with altered expression of genes and pathways important to COPD, such as the Nrf2 oxidative response pathway. Conclusions: DNA methylation is likely an important mechanism contributing to modulation of genes important to COPD pathology. Since these methylation events may underlie disease-specific gene-expression changes, their characterization is a critical first step towards the development of epigenetic markers and an opportunity for developing novel epigenetic therapeutic interventions for COPD. Bisulphite converted DNA from small airway (airways less than <2 mm in diameter) from 38 former smokers: 15 subjects with COPD (post bronchodilator FEV1/FVC ratio <70% and FEV1 predicted ≤ 80%) and 21 with normal lung function, were hybridized to the Illumina Infinium 27k Human Methylation Beadchip.

ORGANISM(S): Homo sapiens  

SUBMITTER: Emily A Vucic   Wan L. Lam 

PROVIDER: E-GEOD-55454 | ArrayExpress | 2014-02-28

SECONDARY ACCESSION(S): GSE55454PRJNA239668

REPOSITORIES: GEO, ArrayExpress

altmetric image

Publications

DNA methylation is globally disrupted and associated with expression changes in chronic obstructive pulmonary disease small airways.

Vucic Emily A EA   Chari Raj R   Thu Kelsie L KL   Wilson Ian M IM   Cotton Allison M AM   Kennett Jennifer Y JY   Zhang May M   Lonergan Kim M KM   Steiling Katrina K   Brown Carolyn J CJ   McWilliams Annette A   Ohtani Keishi K   Lenburg Marc E ME   Sin Don D DD   Spira Avrum A   Macaulay Calum E CE   Lam Stephen S   Lam Wan L WL  

American journal of respiratory cell and molecular biology 20140501 5


DNA methylation is an epigenetic modification that is highly disrupted in response to cigarette smoke and involved in a wide spectrum of malignant and nonmalignant diseases, but surprisingly not previously assessed in small airways of patients with chronic obstructive pulmonary disease (COPD). Small airways are the primary sites of airflow obstruction in COPD. We sought to determine whether DNA methylation patterns are disrupted in small airway epithelia of patients with COPD, and evaluate wheth  ...[more]

Similar Datasets

| GSE111396 | GEO
| GSE56341 | GEO
2014-03-28 | E-GEOD-56341 | ArrayExpress
| GSE64614 | GEO
2006-11-21 | GSE4498 | GEO
2005-10-30 | GSE3320 | GEO
2007-09-06 | E-GEOD-3320 | ArrayExpress
| PRJNA239668 | ENA
| GSE5058 | GEO
2009-04-25 | E-GEOD-5057 | ArrayExpress