Novel candidate blood‐based transcriptional biomarkers of machado‐joseph disease. Issue 7 (25th April 2015)

• Record Type: Journal Article
• Authors: Raposo, Mafalda; Bettencourt, Conceição; Maciel, Patrícia; Gao, Fuying; Ramos, Amanda; Kazachkova, Nadiya; Vasconcelos, João; Kay, Teresa; Rodrigues, Ana João; Bettencourt, Bruno; Bruges‐Armas, Jácome; Geschwind, Daniel; Coppola, Giovanni; Lima, Manuela
• Is Part Of: Movement disorders. Volume 30:Issue 7(2015)
• Page Start: 968
• Page End: 975
• Publication Date: 2015-04-25
• Subjects: Movement disorders -- Periodicals; 610
• DOI: 10.1002/mds.26238
• Languages: English
• ISSNs: 0885-3185

Abstract

<abstract abstract-type="main"> <title>ABSTRACT</title> <sec id="mds26238-sec-0101" sec-type="section"> <title>Background</title> <p>Machado‐Joseph disease (or spinocerebellar ataxia type 3) is a late‐onset polyglutamine neurodegenerative disorder caused by a mutation in the <italic>ATXN3</italic> gene, which encodes for the ubiquitously expressed protein ataxin‐3. Previous studies on cell and animal models have suggested that mutated ataxin‐3 is involved in transcriptional dysregulation. Starting with a whole‐transcriptome profiling of peripheral blood samples from patients and controls, we aimed to confirm abnormal expression profiles in Machado‐Joseph disease and to identify promising up‐regulated genes as potential candidate biomarkers of disease status.</p> </sec> <sec id="mds26238-sec-0601" sec-type="section"> <title>Methods</title> <p>The Illumina Human V4‐HT12 array was used to measure transcriptome‐wide gene expression in peripheral blood samples from 12 patients and 12 controls. Technical validation and validation in an independent set of samples were performed by quantitative real‐time polymerase chain reaction (PCR).</p> </sec> <sec id="mds26238-sec-0701" sec-type="section"> <title>Results</title> <p>Based on the results from the microarray, twenty six genes, found to be up‐regulated in patients, were selected for technical validation by quantitative real‐time PCR (validation rate of 81% for the up‐regulation trend). Fourteen of these were further tested in an independent set of 42 patients and 35 controls; 10 genes maintained the up‐regulation trend (<italic>FCGR3B</italic>, <italic>CSR2RA</italic>, <italic>CLC</italic>, <italic>TNFSF14, SLA, P2RY13, FPR2, SELPLG, YIPF6, </italic> and <italic>GPR96</italic>); <italic>FCGR3B, P2RY13, </italic> and <italic>SELPLG</italic> were significantly up‐regulated in patients when compared with controls.</p> </sec> <sec id="mds26238-sec-0201" sec-type="section"> <title>Conclusions</title> <p>Our findings support the hypothesis that mutated ataxin‐3 is associated with transcription dysregulation, detectable in peripheral blood cells. Furthermore, this is the first report suggesting a pool of up‐regulated genes in Machado‐Joseph disease that may have the potential to be used for fine phenotyping of this disease. © 2015 International Parkinson and Movement Disorder Society</p> </sec> </abstract>