DNA Methylation is Globally Disrupted and Associated with Expression Changes in COPD Small Airways
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Wan Lam
PROVIDER: E-GEOD-56342 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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]
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Project description: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 M-bM-^IM-$ 80%) and 21 with normal lung function, were hybridized to the Illumina Infinium 27k Human Methylation Beadchip.
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Project description:Gene expression profiles in this submission were part of an integrative DNA methylation and gene expression integrative study. The goal of this study was to determine whether DNA methylation patterns were disrupted in small airway epithelia of patients with Chronic Obstructive Pulmonary Disease (COPD) compared to airways from subjects with normal lung function. No subject has cancer or asthma at time of collection. Corresponding DNA methylation profiles for these subjects can be found at GSE55454. We concluded that methylation alterations in COPD airways may underlie disease-specific gene-expression changes (such as the Nrf2 oxidative response pathway). RNA isolated from bronchial brushings was processed and hybridized to Affymetrix Human Gene 1.0 ST Arrays. DNA isolated from these same samples can be found at GSE55454
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