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Series GSE20250 Query DataSets for GSE20250
Status Public on Aug 26, 2019
Title CNV Polymorphisms Modulate the Expression of GST Subtypes in the Human Small Airway Epithelium and Alveolar Macrophages
Organism Homo sapiens
Experiment type Expression profiling by array
Genome variation profiling by SNP array
Summary The glutathione S-transferase (GST) gene family codes for enzymes that detoxify xenobiotics by catalyzing the conjugation of xenobiotics to glutathione. Based on reports that inherited copy number variations (CNV) in the genome modulate some GST expression levels and with the knowledge that cigarette smoke contains >3000 xenobiotics, and that the small airway epithelium and alveolar macrophages are involved early in the pathogensis of smoking-induced lung disease, we asked: do germline CNVs modulate GST expression level in the small airway epithelium and alveolar macrophages? Affymetrix HG U133 Plus 2.0 microarrays were used to survey GST gene expression in the small airway epithelium and alveolar macrophages obtained by bronchoscopic brushings from current smokers (n=35) and nonsmokers (n=35). The CNV genotypes of these 70 subjects were determined by Affymetrix Human SNP array 5.0 chips. Sixteen % of subjects had deletions of both GSTM1 alleles. These deletions were associated with reduced GSTM1 mRNA levels in both the small airway epithelium (p<10-7) and alveolar macrophages (p<0.05). Thirty % of subjects had homozygous deletions of GSTT1 with concomitant reduced mRNA levels in both small airway epithelium and alveolar macrophages (p<10-7). In contrast, genes flanking the CNV regions of both GST genes showed no difference in expression level among subjects with and without the GST deletions (p>0.3). Interestingly, GSTT2B, a duplicate gene of GSTT2, exhibited homozygous deletion in blood in 27% of subjects and was not expressed in small airway epithelium in the remainder of subjects but was expressed in alveolar macrophages of heterozygotes and wild type subjects, proportionate to genotype (p<10-3). These data demonstrate that highly prevalent CNV deletions of genes critical to ameliorating smoking-associated xenobiotic-induced damage in the lung can result in significant modulation of the gene expression levels, with the linear relationship of genotype to expression level suggesting minimal compensation of gene expression levels in heterozygotes consistent with GST polymorphisms playing a role in the risk for development of smoking-induced lung disease.
Overall design Small airway epithelium (from 35 healthy nonsmokers and 35 healthy smokers) and alveolar macrophages (from a subset of the 70 subjects: 22 nonsmokers and 34 smokers) were collected at bronchoscopy, and in conjunction with their blood samples, were used to assess the influence of common heritable copy number polymorphisms in glutathione S-transferase (GST) genes, on microarray and RT-PCR-assessed GST gene expression in human tissues that are relevant to the pathogenesis of smoke-induced lung disease.
Contributor(s) Butler MW, Hackett NR, Salit J, Strulovici-Barel Y, Crystal RG
Citation(s) 21349909
Submission date Feb 09, 2010
Last update date Aug 26, 2019
Contact name Yael Strulovici-Barel
Organization name Weill Cornell Medical College
Department Department of Genetic Medicine
Lab Crystal
Street address 1300 York Avenue
City New York
State/province NY
ZIP/Postal code 10021
Country USA
Platforms (2)
GPL570 [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array
GPL6804 [GenomeWideSNP_5] Affymetrix Genome-Wide Human SNP 5.0 Array
Samples (211)
GSM101095 small airways, non-smoker 001, RMA and MAS
GSM101096 small airways, non-smoker 004, RMA and MAS
GSM101097 small airways, non-smoker 002, RMA and MAS
BioProject PRJNA124215

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Supplementary file Size Download File type/resource
GSE20250_RAW.tar 4.9 Gb (http)(custom) TAR (of CEL, CHP)
Processed data included within Sample table
Processed data provided as supplementary file

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