title: Variability of antioxidant-related gene expression in the airway epithelium of cigarette smokers.
abstract: Cigarette smoking is the major risk factor for developing chronic bronchitis, yet only 15-20% of smokers develop this disorder. Because 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 four categories (catalase/superoxide dismutase family; glutathione metabolism; redox balance; and pentose phosphate cycle) in bronchoscopy-obtained airway epithelium of matched cohorts (13 current smokers, 9 nonsmokers), none of whom had lung disease. There was minimal variation in gene expression levels within the same individual (right versus left lung or over time), but significant upregulation of 16/44 antioxidant-related genes in smoker epithelium compared with nonsmokers. 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.
authors.affiliation: Belfer Gene Therapy Core Facility, Department of Genetic Medicine, Weill Medical College of Cornell University, New York, New York 10021, USA.
authors.forename: Neil R
authors.initials: NR
authors.lastname: Hackett
authors.forename: Adriana
authors.initials: A
authors.lastname: Heguy
authors.forename: Ben-Gary
authors.initials: BG
authors.lastname: Harvey
authors.forename: Timothy P
authors.initials: TP
authors.lastname: O'Connor
authors.forename: Karsta
authors.initials: K
authors.lastname: Luettich
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Flieder
authors.forename: Rana
authors.initials: R
authors.lastname: Kaplan
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Crystal
mesh_terms: D000328:Adult; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D016000:Cluster Analysis; D015331:Cohort Studies; D018076:DNA, Complementary / Q000378:metabolism; D015536:Down-Regulation; D004848:Epithelium / Q000473:pathology*; D005260:Female; D015870:Gene Expression; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D008168:Lung / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D016877:Oxidants / Q000737:chemistry; D010084:Oxidation-Reduction; D010641:Phenotype; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics / Q000473:pathology; D018075:RNA, Complementary / Q000378:metabolism; D012907:Smoking; D015854:Up-Regulation
chemical_list: D000975:Antioxidants; D018076:DNA, Complementary; D016877:Oxidants; D018075:RNA, Complementary