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

164 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

Fingerprint

Gene expression
Tobacco Products
Epithelium
Antioxidants
Genes
Gene Expression
Smoking
Chronic Bronchitis
Up-Regulation
Pentoses
Pulmonary diseases
Bronchoscopy
Microarray Analysis
Microarrays
Genetic Markers
Oxidants
Metabolism
Catalase
Lung Diseases
Superoxide Dismutase

ASJC Scopus subject areas

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

Cite this

Variability of antioxidant-related gene expression in the airway epithelium of cigarette smokers. / Hackett, Neil R.; Heguy, Adriana; Harvey, Ben Gary; O'Connor, Timothy P.; Luettich, Karsta; Flieder, Douglas B.; Kaplan, Rana; Crystal, Ronald.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 29, No. 3 I, 01.09.2003, p. 331-343.

Research output: Contribution to journalArticle

Hackett, Neil R. ; Heguy, Adriana ; Harvey, Ben Gary ; O'Connor, Timothy P. ; Luettich, Karsta ; Flieder, Douglas B. ; Kaplan, Rana ; Crystal, Ronald. / Variability of antioxidant-related gene expression in the airway epithelium of cigarette smokers. In: American Journal of Respiratory Cell and Molecular Biology. 2003 ; Vol. 29, No. 3 I. pp. 331-343.
@article{78639e71edc24bbcb894a5b88a2e47ba,
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.",
author = "Hackett, {Neil R.} and Adriana Heguy and Harvey, {Ben Gary} and O'Connor, {Timothy P.} and Karsta Luettich and Flieder, {Douglas B.} and Rana Kaplan and Ronald Crystal",
year = "2003",
month = "9",
day = "1",
doi = "10.1165/rcmb.2002-0321OC",
language = "English",
volume = "29",
pages = "331--343",
journal = "American Journal of Respiratory Cell and Molecular Biology",
issn = "1044-1549",
publisher = "American Thoracic Society",
number = "3 I",

}

TY - JOUR

T1 - Variability of antioxidant-related gene expression in the airway epithelium of cigarette smokers

AU - Hackett, Neil R.

AU - Heguy, Adriana

AU - Harvey, Ben Gary

AU - O'Connor, Timothy P.

AU - Luettich, Karsta

AU - Flieder, Douglas B.

AU - Kaplan, Rana

AU - Crystal, Ronald

PY - 2003/9/1

Y1 - 2003/9/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0042831342&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0042831342&partnerID=8YFLogxK

U2 - 10.1165/rcmb.2002-0321OC

DO - 10.1165/rcmb.2002-0321OC

M3 - Article

C2 - 12702543

AN - SCOPUS:0042831342

VL - 29

SP - 331

EP - 343

JO - American Journal of Respiratory Cell and Molecular Biology

JF - American Journal of Respiratory Cell and Molecular Biology

SN - 1044-1549

IS - 3 I

ER -