Variability of antioxidant-related gene expression in the airway epithelium of cigarette smokers

Am J Respir Cell Mol Biol. 2003 Sep;29(3 Pt 1):331-43. doi: 10.1165/rcmb.2002-0321OC. Epub 2003 Apr 17.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Antioxidants / metabolism
  • Antioxidants / pharmacology*
  • Cluster Analysis
  • Cohort Studies
  • DNA, Complementary / metabolism
  • Down-Regulation
  • Epithelium / pathology*
  • Female
  • Gene Expression Regulation
  • Gene Expression*
  • Genetic Predisposition to Disease
  • Genetic Variation
  • Humans
  • Lung / metabolism*
  • Male
  • Middle Aged
  • Nucleic Acid Hybridization
  • Oligonucleotide Array Sequence Analysis
  • Oxidants / chemistry
  • Oxidation-Reduction
  • Phenotype
  • Pulmonary Disease, Chronic Obstructive / genetics
  • Pulmonary Disease, Chronic Obstructive / pathology
  • RNA, Complementary / metabolism
  • Smoking*
  • Up-Regulation


  • Antioxidants
  • DNA, Complementary
  • Oxidants
  • RNA, Complementary