Title: Genomic copy number determines functional expression of {beta}-defensin 2 in airway epithelial cells and associates with chronic obstructive pulmonary disease
Authors: Janssens, Wim ×
Nuytten, Hilde
Dupont, Lieven
Van Eldere, Johan
Vermeire, Severine
Lambrechts, Diether
Nackaerts, Kristiaan
Decramer, Marc
Cassiman, Jean-Jacques
Cuppens, Harry #
Issue Date: Jul-2010
Publisher: American Lung Association
Series Title: American Journal of Respiratory and Critical Care Medicine vol:182 issue:2 pages:163-169
Abstract: RATIONALE: Copy number variations of the cluster of beta-defensin genes have been associated with psoriasis and inflammatory bowel disease. Controversy still exists on whether the beta-defensins genes determine susceptibility for chronic obstructive pulmonary disease (COPD). Objectives: We investigated whether genomic copy number variations of the beta-defensin gene cluster have a functional role in airway epithelial cells and associate with the presence of COPD. METHODS: Baseline and inflammatory induced transcript expression of DEFB4 was studied in nasal epithelial cell cultures and its effect on Pseudomonas aeruginosa inhibition was assessed. Subsequently, relevant functional cut-offs for copy numbers were used to explore associations with COPD in two independent case-control studies. MEASUREMENTS AND MAIN RESULTS: Copy number variation in the beta-defensin encoding genes correlated with baseline mRNA DEFB4 expression levels (R(2) = 0.96; P = 0.02), with a plateau effect from five copies or more. Only when higher copy numbers of beta-defensin genes were present, transcription was significantly up-regulated by tumor necrosis factor-alpha (P < 0.0001), which resulted in better antimicrobial activity in vitro. When comparing healthy smokers with COPD patients, a copy number greater than or equal to 5 was associated with increased risk for COPD with an adjusted odds ratio of 1.8 (confidence interval, 1.1-2.8; P = 0.02), which was confirmed by a second independent case-control study. CONCLUSIONS: Genomic copy number variation of beta-defensin encoding genes has a functional role in airway epithelial cells, which may contribute to the pathogenesis of COPD.
ISSN: 1073-449X
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Human Genetics - miscellaneous
Laboratory for Experimental and Clinical Microbiology (-)
Vesalius Research Centre (-)
Laboratory of Clinical Bacteriology and Mycology
Forensic Biomedical Sciences
Laboratory of Translational Genetics (Vesalius Research Center) (+)
× corresponding author
# (joint) last author

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