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Published ahead of print on April 17, 2003, doi:10.1165/rcmb.2002-0321OC

Am. J. Respir. Cell Mol. Biol., Volume 29, Number 3, September 2003, 331-343

A more recent version of this article appeared on September 1, 2003
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Submitted on January 2, 2003
Revised on April 14, 2003

Variability of Antioxidant-related Gene Expression in the Airway Epithelium of Cigarette Smokers

Neil R Hackett1, Adriana Heguy1, Ben-Gary Harvey2, Timothy P O'Connor1, Karsta Luettich3, Douglas B Flieder4, Rana Kaplan2, and Ronald G Crystal5*

1 Belfer Gene Therapy Core Facility, Weill Medical College of Cornell University, New York, NY, USA; Department of Genetic Medicine, Weill Medical College of Cornell University, New York, NY, USA, 2 Division of Pulmonary and Critical Care Medicine, Weill Medical College of Cornell University, New York, NY, USA, 3 Belfer Gene Therapy Core Facility, Weill Medical College of Cornell University, New York, NY, USA, 4 Department of Pathology, Weill Medical College, New York, NY, USA, 5 Belfer Gene Therapy Core Facility, Weill Medical College of Cornell University, New York, NY, USA; Department of Genetic Medicine, Weill Medical College of Cornell University, New York, NY, USA; Division of Pulmonary and Critical Care Medicine, Weill Medical College of Cornell University, New York, NY, USA

* To whom correspondence should be addressed. E-mail: rgcryst{at}med.cornell.edu.

Cigarette smoking is the major risk factor for developing chronic bronchitis, yet only 15-20% of smokers develop this disorder. Since oxidants are the major mechanism of smoking-induced airway damage, we hypothesized that smoking is associated with upregulation of various antioxidant-related genes in the airway epithelium, but the magnitude of the response shows high inter-individual variability. Microarray analysis was used to assess levels of expression of 44 antioxidant-related genes in 4 categories (catalase/superoxide dismutase family; glutathione metabolism; redox balance) in bronchoscopy-obtained airway epithelium of matched cohorts (13 current smokers, 9 non-smokers), none of whom had lung disease. There was minimal variation in gene expression levels within the same individual (right vs left lung or over time), but significant upregulation of 16/44 antioxidant-related genes in smoker epithelium compared to non-smokers. Subgroups of smokers were identified with clusters of expression levels of antioxidant-related genes. We propose that the antioxidant-related genes demonstrating the most variability in the level of expression in smokers may be useful genetic markers in epidemiologic studies assessing susceptibility to smoking-induced chronic bronchitis.




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