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| Status |
Public on Aug 01, 2009 |
| Title |
Expression data from relapsing-remitting MS samples |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
One of our new major finding among the genes that contributes to MS susceptibility is ICSBP1. The so called disease modifying therapies like interferon-beta (IFN-β), possibly acting on the peripheral T-cells, reduce the disease activity and the clinical progression, with a MRI-detectable effect in preventing lesion burden and cerebral atrophy development in RR-MS. It suggests a critical role of peripheral blood mononuclear cells (PBMCs) immune response and modulation in developing inflammation in the brain. We tested the hypothesis that the genetic effect of the susceptible allele ICSBP1 can impact the gene expression profile of molecules belonging to the interferon pathway. We therefore interrogated the PBMC for changes in gene expression profile. We correlate those changes with the minor allele frequency for ICSBP1, performing independent quantitative trait analysis for each treatment category. Expression Quantitative Trait Loci Association with a p value < 0.05 have been used in follow up analysis. The regression coefficient of the Quantitative trait association represents the degree of correlation between the gene expression for each interrogated target gene and the minor allele frequency of the SNP for our gene of interest. This coefficient has been used as input in the subsequent Gene Set Enrichment Analysis performed in a pre-ranked approach. The resulting GSEA-SNP method rests on the assumption that SNPs underlying a disease phenotype might affect genes constituting a signaling pathway or genes with a common regulation. Therefore, GSEA-SNP can facilitate the identification of pathways or of underlying biological mechanisms.
We used microarrays to capture gene expression profile of untreated subjects and of subjects under disease modyfing treatment (Interferon Beta and Glatiramer Acetate), in order to correlate gene expression and genotype data and in order to identify sets of genes specifically regulated in the different treatment categories.
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| Overall design |
Between July 2002 and October 2007, PBMC samples were collected from relapsing-remitting MS subjects and CIS subjects as part of the Comprehensive Longitudinal Investigation of MS at the Brigham & Women’s Hospital (CLIMB study). We then selected the first time point for each subject with multiple measurements based on an at least three months of treatment criteria. We thereafter analyzed the data for each treament category.
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| Contributor(s) |
De Jager PL, Ottoboni L, Hu X |
| Citation(s) |
19525953, 23019656, 23522783 |
| |
| Submission date |
May 22, 2009 |
| Last update date |
Mar 25, 2019 |
| Contact name |
Philip De Jager |
| E-mail(s) |
pdejager@rics.bwh.harvard.edu
|
| Organization name |
The Broad Institute of MIT and Harvard
|
| Street address |
7 Cambridge Center
|
| City |
Cambridge |
| State/province |
MA |
| ZIP/Postal code |
02142 |
| Country |
USA |
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| Platforms (1) |
| GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
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| Samples (240)
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| Relations |
| BioProject |
PRJNA117153 |
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