Genes and gene ontologies common to airflow obstruction and emphysema in the lungs of patients with COPD

Savarimuthu Francis, Santiyagu M., Larsen, Jill E., Pavey, Sandra J., Duhig, Edwina E., Clarke, Belinda E., Bowman, Rayleen V., Hayward, Nick K., Fong, Kwun M. and Yang, Ian A. (2011) Genes and gene ontologies common to airflow obstruction and emphysema in the lungs of patients with COPD. PLoS One, 6 3: . doi:10.1371/journal.pone.0017442


Author Savarimuthu Francis, Santiyagu M.
Larsen, Jill E.
Pavey, Sandra J.
Duhig, Edwina E.
Clarke, Belinda E.
Bowman, Rayleen V.
Hayward, Nick K.
Fong, Kwun M.
Yang, Ian A.
Title Genes and gene ontologies common to airflow obstruction and emphysema in the lungs of patients with COPD
Journal name PLoS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2011-03
Sub-type Article (original research)
DOI 10.1371/journal.pone.0017442
Open Access Status DOI
Volume 6
Issue 3
Total pages 7
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Collection year 2012
Language eng
Formatted abstract
Chronic obstructive pulmonary disease (COPD) is a major public health problem with increasing prevalence worldwide. The primary aim of this study was to identify genes and gene ontologies associated with COPD severity. Gene expression profiling was performed on total RNA extracted from lung tissue of 18 former smokers with COPD. Class comparison analysis on mild (n = 9, FEV1 80–110% predicted) and moderate (n = 9, FEV1 50–60% predicted) COPD patients identified 46 differentially expressed genes (p<0.01), of which 14 genes were technically confirmed by quantitative real-time-PCR. Biological replication in an independent test set of 58 lung samples confirmed the altered expression of ten genes with increasing COPD severity, with eight of these genes (NNMT, THBS1, HLA-DPB1, IGHD, ETS2, ELF1, PTGDS and CYRBD1) being differentially expressed by greater than 1.8 fold between mild and moderate COPD, identifying these as candidate determinants of COPD severity. These genes belonged to ontologies potentially implicated in COPD including angiogenesis, cell migration, proliferation and apoptosis. Our secondary aim was to identify gene ontologies common to airway obstruction, indicated by impaired FEV1 and KCO. Using gene ontology enrichment analysis we have identified relevant biological and molecular processes including regulation of cell-matrix adhesion, leukocyte activation, cell and substrate adhesion, cell adhesion, angiogenesis, cell activation that are enriched among genes involved in airflow obstruction. Exploring the functional significance of these genes and their gene ontologies will provide clues to molecular changes involved in severity of COPD, which could be developed as targets for therapy or biomarkers for early diagnosis.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Article # e17442

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
School of Medicine Publications
 
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Created: Thu, 01 Sep 2011, 12:23:56 EST by Dr Ian Yang on behalf of Medicine - Prince Charles Hospital