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Blood transcriptomics of drug-naive sporadic Parkinson's disease patients.

ABSTRACT: 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.Changes in gene expression in the blood of 40 sporadic PD patients and 20 healthy controls ("Discovery set") were analyzed by taking advantage of the Affymetrix platform. Patients were at the onset of motor symptoms and before initiating any pharmacological treatment. Data analysis was performed by applying Ranking-Principal Component Analysis, PUMA and Significance Analysis of Microarrays. Functional annotations were assigned using GO, DAVID, GSEA to unveil significant enriched biological processes in the differentially expressed genes. The expressions of selected genes were validated using RT-qPCR and samples from an independent cohort of 12 patients and controls ("Validation set").Gene expression profiling of blood samples discriminates PD 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 as CBX5, TCF3, MAN1C1 and DOCK10 were validated by RT-qPCR.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.

SUBMITTER: Calligaris R

PROVIDER: S-EPMC4625854 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Blood transcriptomics of drug-naïve sporadic Parkinson's disease patients.

Calligaris Raffaella R Banica Mihaela M Roncaglia Paola P Robotti Elisa E Finaurini Sara S Vlachouli Christina C Antonutti Lucia L Iorio Francesco F Carissimo Annamaria A Cattaruzza Tatiana T Ceiner Andrea A Lazarevic Dejan D Cucca Alberto A Pangher Nicola N Marengo Emilio E di Bernardo Diego D Pizzolato Gilberto G Gustincich Stefano S

BMC genomics 20151028

<h4>Background</h4>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.<h4>Methods</h4>Changes in gene expression in the blood of 40 sporadic PD patients and 20 healthy controls ("Disco ...[more]

PMID: 26510930

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Project description: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. 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).

Dataset Information

Blood transcriptomics of drug-naive sporadic Parkinson's disease patients.

Publications

Blood transcriptomics of drug-naïve sporadic Parkinson's disease patients.

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