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Status |
Public on Oct 15, 2012 |
Title |
Peripheral blood gene expression changes during allergen inhalation challenge in atopic asthmatic individuals |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
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Summary |
Background: Allergen inhalation challenge in mild asthmatics induces airflow obstruction, airway hyperresponsiveness and inflammation, providing a model for hypothesis-generating experiments to understand regulation of these responses. We have sought to evaluate the peripheral whole blood transcriptome, post-challenge compared to pre-challenge, and to determine the effect of globin mRNA reduction methodology. Methods: Asthmatic subjects (20-60 years of age, with stable, mild allergic asthma, n=17) underwent allergen inhalation challenges. All subjects had an early asthmatic response of ≥ 20% fall in FEV1; most had a late phase response of ≥ 15% fall in FEV1. Blood was collected immediately prior to, and two hours after allergen challenge. Transcriptome analysis was performed using Affymetrix GeneChip® Human Gene 1.0 ST arrays, with and without globin mRNA reduction (PAX-GR and PAX-NGR, respectively) in 4 subjects. Replication studies for expression of nine genes contributing to the top canonical pathway, Nrf2-mediated oxidative stress response pathway, were performed with 5 independent subjects with microarray data, also with the same 4 subjects had microarray results and 8 other independent subjects with QPCR. Data were analyzed using paired t-test and Partek® Genomics Suite™. Results: The number of differentially expressed probe sets from PAX-NGR samples was twice that of PAX-GR samples. Paired analysis of each subjects' pre- and post-sample additionally demonstrated twice the power to detect differentially expressed probe sets. The Nrf2-mediated oxidative stress response pathway was identified as the top canonical pathway in the PAX-NGR samples. ATP-binding cassette sub-family C member 1 (ABCC1) gene was significantly reduced two hours after allergen challenge in the 5 subjects’ microarray dataset and the 2 QPCR replication datasets with P < 0.05. Conclusions: Globin mRNA reduction does not provide benefits to detect differentially expressed genes during allergen inhalation challenge. Allergen inhalation challenge is associated with decreased peripheral blood cell transcript level of ABCC1 gene.
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Overall design |
26 array were analyzed. We first identified differentially expreed genes between post- and pre-challenge samples from 4 asthmatic subjects by using globin reduction samples and non-globin reduction samples (16 arrays). Then we replicated our findings using 10 arrays from 5 asthmatic subjects challenged with allergen. Includes 4 normal blood samples.
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Contributor(s) |
Kam S, He J, Ruan J, Gauvreau GM, O'Byrne PM, FitzGerald MJ, Tebbutt SJ |
Citation(s) |
22316092 |
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Submission date |
Oct 18, 2010 |
Last update date |
Jun 07, 2024 |
Contact name |
Scott Tebbutt |
E-mail(s) |
[email protected]
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Organization name |
University of British Columbia
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Department |
Medicine
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Lab |
James Hogg Research Centre
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Street address |
Room 166, 1081 Burrard Street
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City |
Vancouver |
State/province |
BC |
ZIP/Postal code |
V6Z 1Y6 |
Country |
Canada |
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Platforms (1) |
GPL6244 |
[HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array [transcript (gene) version] |
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Samples (30)
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GSM609423 |
Blood pre non-depleted, biological rep 1 |
GSM609424 |
Blood post non-depleted, biological rep 1 |
GSM609425 |
Blood pre non-depleted, biological rep 2 |
GSM609426 |
Blood post non-depleted, biological rep 2 |
GSM609427 |
Blood pre non-depleted, biological rep 3 |
GSM609428 |
Blood post non-depleted, biological rep 3 |
GSM609429 |
Blood pre non-depleted, biological rep 4 |
GSM609430 |
Blood post non-depleted, biological rep 4 |
GSM609431 |
Blood pre depleted, biological rep 1 |
GSM609432 |
Blood post depleted, biological rep 1 |
GSM609433 |
Blood pre depleted, biological rep 2 |
GSM609434 |
Blood post depleted, biological rep 2 |
GSM609435 |
Blood pre depleted, biological rep 3 |
GSM609436 |
Blood post depleted, biological rep 3 |
GSM609437 |
Blood pre depleted, biological rep 4 |
GSM609438 |
Blood post depleted, biological rep 4 |
GSM610428 |
Blood pre EDTA, biological rep 1 |
GSM610429 |
Blood post EDTA, biological rep 1 |
GSM610430 |
Blood pre EDTA, biological rep 2 |
GSM610431 |
Blood post EDTA, biological rep 2 |
GSM610432 |
Blood pre EDTA, biological rep 3 |
GSM610433 |
Blood post EDTA, biological rep 3 |
GSM610434 |
Blood pre EDTA, biological rep 4 |
GSM610435 |
Blood post EDTA, biological rep 4 |
GSM610436 |
Blood pre EDTA, biological rep 5 |
GSM610437 |
Blood post EDTA, biological rep 5 |
GSM745604 |
Blood normal, biological rep 1 |
GSM745605 |
Blood normal, biological rep 2 |
GSM745606 |
Blood normal, biological rep 3 |
GSM745607 |
Blood normal, biological rep 4 |
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Relations |
BioProject |
PRJNA132141 |
Supplementary file |
Size |
Download |
File type/resource |
GSE24745_RAW.tar |
119.1 Mb |
(http)(custom) |
TAR (of CEL) |
Processed data included within Sample table |
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