 |
 |
GEO help: Mouse over screen elements for information. |
|
| 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 |
| E-mail(s) |
yas2003@med.cornell.edu
|
| 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 |
| GSM101098 |
small airways, non-smoker 003, RMA and MAS |
| GSM101100 |
small airways, non-smoker 006, RMA and MAS |
| GSM101101 |
small airways, non-smoker 021, RMA and MAS |
| GSM101102 |
small airways, non-smoker 019, RMA and MAS |
| GSM101103 |
small airways, non-smoker 014, RMA and MAS |
| GSM101104 |
small airways, non-smoker 008, RMA and MAS |
| GSM101105 |
small airways, non-smoker 015, RMA and MAS |
| GSM101106 |
small airways, non-smoker 005, RMA and MAS |
| GSM101111 |
small airways, smoker 001, RMA and MAS |
| GSM101113 |
small airways, smoker 048, RMA and MAS |
| GSM101114 |
small airways, smoker 041, RMA and MAS |
| GSM101115 |
small airways, smoker 044, RMA and MAS |
| GSM101116 |
small airways, smoker 049, RMA and MAS |
| GSM114090 |
small airways, smoker 063, MAS5 |
| GSM190149 |
Small airways, non-smoker 011 |
| GSM190150 |
Small airways, non-smoker 029 |
| GSM190151 |
small airways, non-smoker 034 |
| GSM190152 |
Small airways, non-smoker 035 |
| GSM190153 |
Small airways, non-smoker 036 |
| GSM190155 |
Small airways, non-smoker 042 |
| GSM190156 |
small airways, non-smoker 044 |
| GSM219241 |
alveolar macrophages, non-smoker 001 |
| GSM219242 |
alveolar macrophages, non-smoker 002 |
| GSM219243 |
alveolar macrophages, non-smoker 003 |
| GSM219244 |
alveolar macrophages, non-smoker 005 |
| GSM219245 |
alveolar macrophages, non-smoker 006 |
| GSM219246 |
alveolar macrophages, non-smoker 008 |
| GSM219247 |
alveolar macrophages, non-smoker 013 |
| GSM219248 |
alveolar macrophages, non-smoker 014 |
| GSM219249 |
alveolar macrophages, non-smoker 019 |
| GSM219250 |
alveolar macrophages, non-smoker 021 |
| GSM219251 |
alveolar macrophages, non-smoker 035 |
| GSM219252 |
alveolar macrophages, smoker 001 |
| GSM219253 |
alveolar macrophages, smoker 002 |
| GSM219254 |
alveolar macrophages, smoker 023 |
| GSM219256 |
alveolar macrophages, smoker 027 |
| GSM219257 |
alveolar macrophages, smoker 033 |
| GSM219258 |
alveolar macrophages, smoker 040 |
| GSM219259 |
alveolar macrophages, smoker 041 |
| GSM219260 |
alveolar macrophages, smoker 044 |
| GSM219261 |
alveolar macrophages, smoker 057 |
| GSM219262 |
alveolar macrophages, smoker 058 |
| GSM219263 |
alveolar macrophages, smoker 063 |
| GSM219264 |
alveolar macrophages, smoker 069 |
| GSM252871 |
small airways, smoker 040 |
| GSM252876 |
small airways, smoker 057 |
| GSM252879 |
small airways, smoker 074 |
| GSM252880 |
small airways, smoker 093 |
| GSM252881 |
small airways, smoker 094 |
| GSM252882 |
small airways, smoker 095 |
| GSM252884 |
small airways, smoker 098 |
| GSM252885 |
small airways, smoker 103 |
| GSM254149 |
small airways, non-smoker 045 |
| GSM254150 |
small airways, non-smoker 059 |
| GSM254151 |
small airways, non-smoker 071 |
| GSM254152 |
small airways, non-smoker 078 |
| GSM254158 |
small airways, smoker 114 |
| GSM254159 |
small airways, smoker 119 |
| GSM254160 |
small airways, smoker 152 |
| GSM254161 |
small airways, smoker 169 |
| GSM298219 |
small airways, non-smoker 039 |
| GSM298220 |
small airways, non-smoker 046 |
| GSM298221 |
small airways, non-smoker 047 |
| GSM298223 |
small airways, non-smoker 050 |
| GSM298224 |
small airways, non-smoker 055 |
| GSM298225 |
small airways, non-smoker 065 |
| GSM298226 |
small airways, non-smoker 072 |
| GSM298227 |
small airways, non-smoker 076 |
| GSM298229 |
small airways, non-smoker 083 |
| GSM298230 |
small airways, smoker 087 |
| GSM298231 |
small airways, smoker 102 |
| GSM298232 |
small airways, smoker 120 |
| GSM298233 |
small airways, smoker 122 |
| GSM298234 |
small airways, smoker 123 |
| GSM298236 |
small airways, smoker 129 |
| GSM298237 |
small airways, smoker 130 |
| GSM298238 |
small airways, smoker 134 |
| GSM298239 |
small airways, smoker 136 |
| GSM298240 |
small airways, smoker 141 |
| GSM298241 |
small airways, smoker 155 |
| GSM298242 |
small airways, smoker 159 |
| GSM298243 |
small airways, smoker 161 |
| GSM298244 |
small airways, smoker 164 |
| GSM298247 |
small airways, smoker 177 |
| GSM300859 |
small airways, non-smoker 085 |
| GSM302396 |
small airways, non-smoker 022 |
| GSM302397 |
small airways, non-smoker 066 |
| GSM302399 |
small airways, smoker 195 |
| GSM349912 |
alveolar macrophages, non-smoker 022 |
| GSM349913 |
alveolar macrophages, non-smoker 023 |
| GSM349914 |
alveolar macrophages, non-smoker 029 |
| GSM349915 |
alveolar macrophages, non-smoker 042 |
| GSM349916 |
alveolar macrophages, non-smoker 045 |
| GSM349917 |
alveolar macrophages, non-smoker 059 |
| GSM349918 |
alveolar macrophages, non-smoker 059_089 |
| GSM349919 |
alveolar macrophages, non-smoker 060 |
| GSM349921 |
alveolar macrophages, non-smoker 066 |
| GSM349922 |
alveolar macrophages, non-smoker 071 |
| GSM349923 |
alveolar macrophages, non-smoker 076 |
| GSM349924 |
alveolar macrophages, non-smoker 083 |
| GSM349925 |
alveolar macrophages, smoker 087 |
| GSM349926 |
alveolar macrophages, smoker 094 |
| GSM349927 |
alveolar macrophages, smoker 103 |
| GSM349929 |
alveolar macrophages, smoker 114 |
| GSM349930 |
alveolar macrophages, smoker 119 |
| GSM349931 |
alveolar macrophages, smoker 120 |
| GSM349932 |
alveolar macrophages, smoker 122 |
| GSM349933 |
alveolar macrophages, smoker 125 |
| GSM349934 |
alveolar macrophages, smoker 129 |
| GSM349935 |
alveolar macrophages, smoker 130 |
| GSM349936 |
alveolar macrophages, smoker 134 |
| GSM349937 |
alveolar macrophages, smoker 136 |
| GSM349938 |
alveolar macrophages, smoker 155 |
| GSM349939 |
alveolar macrophages, smoker 159 |
| GSM349940 |
alveolar macrophages, smoker 161 |
| GSM349941 |
alveolar macrophages, smoker 164 |
| GSM349942 |
alveolar macrophages, smoker 177 |
| GSM349943 |
alveolar macrophages, smoker 183 |
| GSM349944 |
alveolar macrophages, smoker 195 |
| GSM350871 |
small airways, non-smoker 094 |
| GSM350874 |
small airways, smoker 188 |
| GSM350875 |
non-smoker 001, genotype |
| GSM350876 |
non-smoker 002, genotype |
| GSM350877 |
non-smoker 003, genotype |
| GSM350878 |
non-smoker 004, genotype |
| GSM350879 |
non-smoker 005, genotype |
| GSM350880 |
non-smoker 006, genotype |
| GSM350881 |
non-smoker 008, genotype |
| GSM350882 |
non-smoker 011, genotype |
| GSM350883 |
non-smoker 014, genotype |
| GSM350884 |
non-smoker 015, genotype |
| GSM350885 |
non-smoker 019, genotype |
| GSM350886 |
small airways, non-smoker 021, genotype |
| GSM350887 |
small airways, non-smoker 022, genotype |
| GSM350888 |
non-smoker 029, genotype |
| GSM350889 |
non-smoker 034, genotype |
| GSM350890 |
non-smoker 035, genotype |
| GSM350891 |
small airways, non-smoker 036, genotype |
| GSM350892 |
non-smoker 039, genotype |
| GSM350893 |
non-smoker 042, genotype |
| GSM350894 |
non-smoker 044, genotype |
| GSM350895 |
non-smoker 045, genotype |
| GSM350896 |
non-smoker 046, genotype |
| GSM350897 |
non-smoker 047, genotype |
| GSM350898 |
small airways, non-smoker 050, genotype |
| GSM350899 |
non-smoker 055, genotype |
| GSM350900 |
non-smoker 059, genotype |
| GSM350901 |
non-smoker 065, genotype |
| GSM350902 |
non-smoker 066, genotype |
| GSM350903 |
non-smoker 071, genotype |
| GSM350904 |
non-smoker 072, genotype |
| GSM350905 |
small airways, non-smoker 076, genotype |
| GSM350906 |
non-smoker 078, genotype |
| GSM350907 |
non-smoker 083, genotype |
| GSM350908 |
non-smoker 085, genotype |
| GSM350910 |
non-smoker 094, genotype |
| GSM350913 |
smoker 001, genotype |
| GSM350914 |
small airways, smoker 027, genotype |
| GSM350915 |
small airways, smoker 033, genotype |
| GSM350916 |
smoker 040, genotype |
| GSM350917 |
smoker 041, genotype |
| GSM350918 |
smoker 044, genotype |
| GSM350919 |
smoker 048, genotype |
| GSM350920 |
smoker 049, genotype |
| GSM350921 |
smoker 057, genotype |
| GSM350922 |
smoker 063, genotype |
| GSM350923 |
small airways, smoker 069, genotype |
| GSM350924 |
smoker 074, genotype |
| GSM350925 |
small airways, smoker 087, genotype |
| GSM350926 |
smoker 093, genotype |
| GSM350927 |
smoker 094, genotype |
| GSM350928 |
smoker 095, genotype |
| GSM350929 |
smoker 098, genotype |
| GSM350930 |
smoker 102, genotype |
| GSM350931 |
smoker 103, genotype |
| GSM350932 |
smoker 114, genotype |
| GSM350933 |
smoker 119, genotype |
| GSM350934 |
smoker 120, genotype |
| GSM350935 |
small airways, smoker 122, genotype |
| GSM350936 |
smoker 123, genotype |
| GSM350937 |
smoker 129, genotype |
| GSM350938 |
smoker 130, genotype |
| GSM350939 |
smoker 134, genotype |
| GSM350940 |
small airways, smoker 136, genotype |
| GSM350941 |
small airways, smoker 141, genotype |
| GSM350942 |
smoker 152, genotype |
| GSM350943 |
smoker 155, genotype |
| GSM350944 |
smoker 159, genotype |
| GSM350945 |
smoker 161, genotype |
| GSM350946 |
smoker 164, genotype |
| GSM350947 |
smoker 169, genotype |
| GSM350949 |
smoker 177, genotype |
| GSM350950 |
small airways, smoker 183, genotype |
| GSM350951 |
small airways, smoker 186, genotype |
| GSM350952 |
smoker 188, genotype |
| GSM350953 |
smoker 195, genotype |
| GSM498335 |
smoker 058, genotype |
| GSM498336 |
smoker 240, genotype |
| GSM507479 |
non-smoker 013, genotype |
| GSM507480 |
non-smoker 023, genotype |
| GSM507481 |
non-smoker 059_089, genotype |
| GSM507482 |
non-smoker 060_090, genotype |
| GSM507483 |
smoker 002, genotype |
| GSM507484 |
smoker 023, genotype |
| GSM507485 |
smoker 125, genotype |
| GSM507486 |
alveolar macrophages, smoker 049 |
| GSM507487 |
alveolar macrophages, smoker 186 |
| GSM507488 |
alveolar macrophages, smoker 240 |
|
| Relations |
| BioProject |
PRJNA124215 |
| 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 |
|
|
|
|
 |
Less...
More...