{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T06:56:35Z","timestamp":1791269795116,"version":"4.1.0"},"reference-count":68,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2014,5,1]],"date-time":"2014-05-01T00:00:00Z","timestamp":1398902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>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 whether changes in gene expression are associated with these disruptions. 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\u2019s Infinium HM27 and Affymetrix\u2019s 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 with and without COPD matched for age, pack-years, and years of smoking cessation. Our results indicate that aberrant DNA methylation is (1) a genome-wide phenomenon in small airways of patients with COPD, and (2) associated with altered expression of genes and pathways important to COPD, such as the NF-E2\u2013related factor 2 oxidative response pathway. DNA methylation is likely an important mechanism contributing to modulation of genes important to COPD pathology. Because these methylation events may underlie disease-specific gene expression changes, their characterization is a critical first step toward the development of epigenetic markers and an opportunity for developing novel epigenetic therapeutic interventions for COPD.<\/jats:p>","DOI":"10.1165\/rcmb.2013-0304oc","type":"journal-article","created":{"date-parts":[[2013,12,3]],"date-time":"2013-12-03T16:23:32Z","timestamp":1386087812000},"page":"912-922","source":"Crossref","is-referenced-by-count":141,"title":["DNA Methylation Is Globally Disrupted and Associated with Expression Changes in Chronic Obstructive Pulmonary Disease Small Airways"],"prefix":"10.1093","volume":"50","author":[{"given":"Emily A.","family":"Vucic","sequence":"first","affiliation":[{"name":"Department of Integrative Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raj","family":"Chari","sequence":"additional","affiliation":[{"name":"Department of Genetics, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelsie L.","family":"Thu","sequence":"additional","affiliation":[{"name":"Department of Integrative Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian M.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Department of Integrative Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison M.","family":"Cotton","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer Y.","family":"Kennett","sequence":"additional","affiliation":[{"name":"Department of Integrative Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"May","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Integrative Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim M.","family":"Lonergan","sequence":"additional","affiliation":[{"name":"Department of Integrative Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrina","family":"Steiling","sequence":"additional","affiliation":[{"name":"Division of Computational Biomedicine, Department of Medicine, Boston University Medical 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