|
Status |
Public on Oct 29, 2015 |
Title |
Blood transcriptomics of drug-naïve sporadic Parkinson’s disease patients |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
|
Summary |
Parkinson's disease (PD) is a chronic progressive neurodegenerative disorder that is clinically defined in terms of motor symptoms. These are preceded by prodromal non-motor manifestations that prove the systemic nature of the disease. Identifying genes and pathways altered in living patients provide new information on the diagnosis and pathogenesis of sporadic PD. We study changes in gene expression in the blood of 40 sporadic PD patients and 20 healthy controls (“Discovery set”) by taking advantage of the Affymetrix platform. Patients were at the onset of motor symptoms and before initiating any pharmacological treatment. By applying Ranking-Principal Component Analysis, PUMA and Significance Analysis of Microarrays, gene expression profiling discriminates patients from healthy controls and identifies differentially expressed genes in blood. The majority of these are also present in dopaminergic neurons of the Substantia Nigra, the key site of neurodegeneration. Together with neuronal apoptosis, lymphocyte activation and mitochondrial dysfunction, already found in previous analysis of PD blood and post-mortem brains, we unveiled transcriptome changes enriched in biological terms related to epigenetic modifications including chromatin remodeling and methylation. Candidate transcripts were validated by RT-qPCR in an independent cohort of 12 patients and controls (“Validation set”). Our data support the use of blood transcriptomics to study neurodegenerative diseases. It identifies changes in crucial components of chromatin remodeling and methylation machineries as early events in sporadic PD suggesting epigenetics as target for therapeutic intervention.
|
|
|
Overall design |
Analyzed samples include blood samples from 40 PD patients and 20 healthy controls.
Of the original 60 samples, one (a control sample) did not pass the microarray hybridization quality controls and was excluded from further analyses. All results of bioinformatics analyses shown in this study refer to this set of 59 samples (reported here).
|
|
|
Contributor(s) |
Roncaglia P |
Citation(s) |
26510930 |
Submission date |
Aug 21, 2015 |
Last update date |
Dec 06, 2018 |
Contact name |
Paola Roncaglia |
Organization name |
SISSA/ISAS (International School for Advanced Studies)
|
Department |
Neurobiology
|
Street address |
via Bonomea 265
|
City |
Trieste |
State/province |
TS |
ZIP/Postal code |
34136 |
Country |
Italy |
|
|
Platforms (1) |
GPL571 |
[HG-U133A_2] Affymetrix Human Genome U133A 2.0 Array |
|
Samples (59)
|
|
Relations |
BioProject |
PRJNA293554 |