Journal Article

Genes and Gene Ontologies Common to Airflow Obstruction and Emphysema in the Lungs of Patients with COPD

Bowman, Rayleen V., Clarke, Belinda E., Pavey, Sandra J., Larsen, Jill E., Duhig, Edwina E., Savarimuthu Francis, Santiyagu M., Yang, Ian A., Hayward, Nick K., Fong, Kwun M.

2011

Overview

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, FEV(1) 80-110% predicted) and moderate (n = 9, FEV(1) 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 FEV(1) 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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Activation / Adhesion / Aged / Air flow / Airflow / Airway management / Analysis / Angiogenesis / Apoptosis / Bioindicators / Biological activity / Biology / Biomarkers / Cell activation / Cell adhesion / Cell migration / Chronic obstructive lung disease / Chronic obstructive pulmonary disease / Data mining / Databases, Genetic / Demography / Disease prevention / Emphysema / Ets-2 protein / Experiments / Female / Gene expression / Gene Expression Regulation / Genes / Genetic aspects / Genetic Association Studies / Genomes / Genomics / Histocompatibility antigen HLA / HLA antigens / Hospitals / Humans / Hyperoxia / Leukemia / Leukocyte migration / Leukocytes / Lung - metabolism / Lung - physiopathology / Lung diseases / Lungs / Male / Mathematical models / Medical research / Medicine / Obstructive lung disease / Ontology / Pathogenesis / Patients / Public health / Pulmonary Disease, Chronic Obstructive - complications / Pulmonary Disease, Chronic Obstructive - genetics / Pulmonary Disease, Chronic Obstructive - physiopathology / Pulmonary Emphysema - complications / Pulmonary Emphysema - genetics / Pulmonary Emphysema - physiopathology / Reproducibility of Results / Respiratory Function Tests / Respiratory tract / Reverse Transcriptase Polymerase Chain Reaction / Ribonucleic acid / RNA / Smoking / Studies / White blood cells