title: Gene expression profile in fibroblasts of Huntington's disease patients and controls.
abstract: Huntington's disease is an inherited disorder caused by expanded stretch of consecutive trinucleotides (cytosine-adenosine-guanine, CAG) within the first exon of the huntingtin (HTT) gene on chromosome 4 (p16.3). The mutated huntingtin (mHTT) gains toxic function, probably through mechanisms that involve aberrant interactions in several pathways, causing cytotoxicity. Pathophysiology of disease involves several tissues; indeed it has been shown that there is a broad toxic effect of mHTT in the peripheral tissue of patients with HD, not only in the central nervous system. In this study we compared gene expression profiles (GEP) of HD fibroblasts and matched controls using microarray technology. We used RT-PCR to test the consistency of the microarray data and we found four genes up-regulated in HD patients with respect to control individuals. The genes appear to be involved in different pathways that have been shown to be perturbed even in HD models and patients. Although our study is preliminary and has to be extended to a larger cohort of HD patients and controls, nevertheless it shows that gene expression profiles seem to be altered in the fibroblasts of HD patients. Validation of the differential expressions at the protein level is required to ascertain if this cell type can be considered a suitable model for the identification of HD biomarkers.
authors.affiliation: Division of Biology and Genetics, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy. Electronic address: marchina@med.unibs.it.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Marchina
authors.affiliation: Division of Biology and Genetics, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Misasi
authors.affiliation: Division of Biology and Genetics, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Bozzato
authors.affiliation: Division of Biology and Genetics, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Ferraboli
authors.affiliation: Division of Neurology, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Agosti
authors.affiliation: Division of Neurology, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Rozzini
authors.affiliation: Division of Biology and Genetics, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Borsani
authors.affiliation: Division of Biology and Genetics, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Barlati
authors.affiliation: Division of Neurology, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Padovani
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000368:Aged; D005260:Female; D005347:Fibroblasts / Q000502:physiology*; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics / Q000473:pathology*; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics; D054799:Phospholipase C beta / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D059467:Transcriptome / Q000502:physiology*; D019680:Trinucleotide Repeat Expansion / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics* / Q000502:physiology; D054460:rho-Associated Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: C555337:APC protein, human; D025601:Adenomatous Polyposis Coli Protein; C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; C502845:UBE3D protein, human; D044767:Ubiquitin-Protein Ligases; C515851:ROCK1 protein, human; D054460:rho-Associated Kinases; C518042:PLCB4 protein, human; D054799:Phospholipase C beta
keywords: Biomarkers; Gene expression profile; Human fibroblasts; Huntingtin; Huntington's disease; Neurodegeneration; PolyQ