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

Neil R. Hackett, Adriana Heguy, Ben Gary Harvey, Timothy P. O'Connor, Karsta Luettich, Douglas B. Flieder, Rana Kaplan, Ronald Crystal

Research output: Contribution to journalArticle

165 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)331-343
Number of pages13
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume29
Issue number3 I
DOIs
Publication statusPublished - 1 Sep 2003
Externally publishedYes

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ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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