Dataset Information

Variability in small airway epithelial gene expression among normal smokers.

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.

SUBMITTER: Ammous Z

PROVIDER: S-EPMC3632367 | biostudies-literature | 2008 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Variability in small airway epithelial gene expression among normal smokers.

Ammous Zeinab Z Hackett Neil R NR Butler Marcus W MW Raman Tina T Dolgalev Igor I O'Connor Timothy P TP Harvey Ben-Gary BG Crystal Ronald G RG

Chest 20080313 6

<h4>Background</h4>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.<h4>Methods</h4>Affymetrix arrays and quantitative polymerase chain reaction were used to assess the variability o ...[more]

PMID: 18339782

Similar Datasets

Project description:Despite overwhelming data that cigarette smoking causes chronic obstructive pulmonary disease (COPD), only a minority of chronic smokers are affected, strongly suggesting that genetic factors modify susceptibility to this disease. We hypothesized that there are individual variations in the response to cigarette smoking, with variability among smokers in expression levels of protective / susceptibility genes. Affymetrix arrays and TaqMan PCR were used to assess the variability of gene expression in the small airway epithelium obtained by fiberoptic bronchoscopy of 18 normal non-smokers, 18 normal smokers and 18 smokers with COPD. We identified 201 probesets representing 150 smoking-responsive genes that were significantly up- 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 probesets and realtime PCR and was observed in both normal smokers and smokers with COPD. There was greater individual variability 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 there is likely genetic diversity within this subset of genes with highly variable individual to individual responses of the small airway epithelium to smoking, and this subset of genes represent putative candidates for assessment of susceptibility/protection from disease for future gene-based epidemiological studies for the risk of smokers for COPD. Experiment Overall Design: Affymetrix arrays and TaqMan PCR were used to assess the variability of gene expression in the small airway epithelium obtained by fiberoptic bronchoscopy of 18 normal non-smokers, 18 normal smokers and 18 smokers with COPD.

Project description:Upregulation of Expression of the Ubiquitin Carboxyl Terminal Hydrolase L1 Gene in Human Airway Epithelium of Cigarette Smokers The microarray data deposited here is from 39 HG-U133 Plus 2.0 GeneChips, from 12 normal non-smokers, 12 phenotypic normal smokers, 9 Early COPD and 6 COPD individuals, all small airways, all small airway. A subset of these samples have been already submitted under GEO Accession Number GSE 4498. These are: 12 non-smokers samples (GSM101095-GSM101106) and 10 smoker samples (GSM101107-GSM101116). These 22 samples that are also in GSE4498 were described in Harvey, B-G; Heguy, A.; Leopold, P.L.; Carolan, B.; Ferris, B. and Crystal R.G. Modification of Gene Expression of the Small Airway Epithelium in Response to Cigarette Smoking. J. Mol. Med (in press). These data are part of a study aimed at understanding how cigarette smoking modifies neuroendocrine cells, in which microarray analysis with TaqMan confirmation was used to assess airway epithelial samples obtained by fiberoptic bronchoscopy from 81 individuals (normal nonsmokers, normal smokers, smokers with early COPD and smokers with established COPD). Of 11 genes considered to be neuroendocrine cell-specific, only ubiquitin C-terminal hydrolase L1(UCHL1), a member of the ubiquitin proteasome pathway, was consistently upregulated in smokers compared to nonsmokers. Up-regulation of UCHL1 at the protein level was observed with immunohistochemistry of bronchial biopsies of smokers compared to nonsmokers. Interestingly, however, while UCHL1 expression was present only in neuroendocrine cells of the airway epithelium in nonsmokers, UCHL1 expression was also expressed in ciliated epithelial cells in smokers, an intriguing observation in light of recent observations that ciliated cells can are capable of transdifferentiating to other airway epithelium. In the context that UCHL1 is involved in the degradation of unwanted, misfolded or damaged proteins within the cell and is overexpressed in >50% of lung cancers, its overexpression in chronic smokers may represent an early event in the complex transformation from normal epithelium to overt malignancy. Keywords: non-smokers vs phenotypic normal smokers, smokers with early COPD, and smokers with COPD

Dataset Information

Variability in small airway epithelial gene expression among normal smokers.

Publications

Variability in small airway epithelial gene expression among normal smokers.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets