GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
Series GSE14895 Query DataSets for GSE14895
Status Public on Feb 17, 2010
Title The trait of MS: Altered transcription regulation of nuclear receptors networks operate in the pre-disease state
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Molecular mechanisms that influence susceptibility to multiple sclerosis are poorly understood. We conducted a gene expression study in healthy subjects that subsequently developed the disease. Gene expression profiles (HG U133A and A2, Affymetrix, 22,215 transcripts) of peripheral blood mononuclear cells were analyzed in 9 healthy subjects (mean age 19.8+1.1 years) up to 9 years (mean 5.1±1.2 years) before onset of MS (MS to be, MS2b), 11 age-, gender-, and origin-matched subjects that remained MS-free (MSf), and 31 clinically isolated syndrome (CIS) patients. Most informative genes (p<0.05) and significant biological processes were compared. 1051 genes (611 up-regulated, 440 down-regulated) were significantly different between MS2b and MSf subjects. MS2b signature was characterized by down-regulation of the nuclear receptor (NR) family genes including NR subfamily 4 group A member1 (NR4A1, p=0.01), member 3 (NR4A3, p=0.01), NR subfamily 2 group F member 2 (NR2F1, p=0.03) and vitamin D receptor (VDR, p=0.02), all known to be involved in T-cell regulation by apoptosis. Comparison between MS2b and CIS operating networks demonstrated evolution of the altered NR dependent apoptosis regulation. Decreased NR4A1 expression was verified at the mRNA and protein level in an independent cohort of 20 relapsing-remitting MS patients. The identified MS trait is associated with suppressed transcription of NR networks that leads to altered apoptosis of activated T cells and the development of clinical disease. MS2b subjects have already an ongoing process that eventually will lead to clinical disease and our finding are of importance as they suggest the possibility of early detection and prevention of MS.

Keywords: disease state analysis
Overall design Blood samples of healthy subjects that later developed MS (MS-to-be, MS2b, N=9) were identified and used for gene expression study. For each sample of MS2b subject, a sample of an age and gender matched subject that remained MS-free (MSf, N=11) was randomly selected. A cohort of 31 CIS patients who gave blood sample for gene expression analysis within 3 months of the onset of their first neurological event, was used for comparison with the MS2b gene expression signature. For establishment of the CIS gene expression signature, microarray data from 13 age- and sex- matched healthy subjects were used.
Contributor(s) Achiron A, Grotto I, alicer R, Magalashvili D, Feldman A, Gurevich M
Citation(s) 20079437
Submission date Feb 18, 2009
Last update date Dec 06, 2018
Contact name Michael Gurevich
Organization name Sheba Medical Center
Department Multiple Sclerosis Center
Lab Neurogenomics and Neuroimmunology
Street address Tel Hashomer
City Ramat Gan
ZIP/Postal code 52621
Country Israel
Platforms (2)
GPL96 [HG-U133A] Affymetrix Human Genome U133A Array
GPL571 [HG-U133A_2] Affymetrix Human Genome U133A 2.0 Array
Samples (64)
GSM372101 MS2b 1
GSM372102 MS2b 2
GSM372103 MS2b 3
BioProject PRJNA111847

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE14895_RAW.tar 154.1 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap