Variability in small airway epithelial gene expression among normal smokers. Academic Article uri icon

Overview

MeSH

  • Adult
  • Analysis of Variance
  • Bronchoscopy
  • Female
  • Gene Expression Regulation
  • Genetic Variation
  • Humans
  • Male
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • Respiratory Function Tests

MeSH Major

  • Gene Expression Profiling
  • Pulmonary Disease, Chronic Obstructive
  • Respiratory Mucosa
  • Smoking

abstract

  • Despite overwhelming data that cigarette smoking causes COPD, only a minority of long-term smokers are affected, strongly suggesting that genetic factors modify susceptibility to this disease. We hypothesized that individual variations exist in the response to cigarette smoking, with variability among smokers in expression levels of protective/susceptibility genes. Affymetrix arrays and quantitative polymerase chain reaction were used to assess the variability of gene expression in the small airway epithelium obtained by fiberoptic bronchoscopy of 18 normal nonsmokers, 18 normal smokers, and 18 smokers with COPD. We identified 201 probe sets representing 152 smoking-responsive genes that were significantly up-regulated or down-regulated, and assessed the coefficient of variation in expression levels among the study population. Variation was a reproducible property of each gene as assessed by different microarray probe sets and real-time polymerase chain reaction, and was observed in both normal smokers and smokers with COPD. Greater individual variability was found in smokers with COPD than in normal smokers. The majority of these highly variable smoking-responsive genes were in the functional categories of signal transduction, xenobiotic degradation, metabolism, transport, oxidant related, and transcription. A similar pattern of the same highly variable genes was observed in an independent data set. We propose that genetic diversity is likely within this subset of genes, with highly variable individual-to-individual responses of the small airway epithelium to smoking, and that this subset of genes represents putative candidates for assessment of susceptibility/protection from disease in future gene-based epidemiologic studies of smokers' risk for COPD.

publication date

  • June 2008

has subject area

  • Adult
  • Analysis of Variance
  • Bronchoscopy
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Genetic Variation
  • Humans
  • Male
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • Pulmonary Disease, Chronic Obstructive
  • Respiratory Function Tests
  • Respiratory Mucosa
  • Smoking

Research

keywords

  • Clinical Trial
  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3632367

Digital Object Identifier (DOI)

  • 10.1378/chest.07-2245

PubMed ID

  • 18339782

Additional Document Info

start page

  • 1344

end page

  • 1353

volume

  • 133

number

  • 6