title: Identification of candidate genes for Parkinson's disease through blood transcriptome analysis in LRRK2-G2019S carriers, idiopathic cases, and controls.
abstract: The commonest known cause of Parkinson's disease (PD) is the G2019S mutation of the LRRK2 gene, but this mutation is not sufficient for causing PD, and many carriers of the mutation never develop PD symptoms during life. Differences at the expression level of certain genes, resulting from either genetic variations or environmental interactions, might be one of the mechanisms underlying differential risks for developing both idiopathic and genetic PD. To identify the genes involved in PD pathogenesis, we compared genome-wide gene expression (RNA-seq) in peripheral blood of 20 PD patients carrying the G2019S mutation of the LRRK2 gene, 20 asymptomatic carriers of the mutation, 20 subjects with idiopathic PD, 20 controls and 7 PD patients before and after initiating dopaminergic therapy. We identified 13 common genes (ADARB2, CEACAM6, CNTNAP2, COL19A1, DEF4, DRAXIN, FCER2, HBG1, NCAPG2, PVRL2, SLC2A14, SNCA, and TCL1B) showing significant differential expression between G2019S-associated PD and asymptomatic carriers and also between idiopathic PD and controls but not between untreated and treated patients. Some of these genes are functionally involved in the processes known to be involved in PD pathogenesis, such as Akt signaling, glucose metabolism, or immunity. We consider that these genes merit further attention in future studies as potential candidate genes involved in both idiopathic and LRRK2-G2019S-associated forms of PD.
authors.affiliation: Service of Neurology, University Hospital Marqués de Valdecilla (IDIVAL), University of Cantabria (UC), Santander, Spain; Centro de Investigación en Red de Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain. Electronic address: jinfante@humv.es.
authors.forename: Jon
authors.initials: J
authors.lastname: Infante
authors.affiliation: Institute of Biomedicine and Biotechnology of Cantabria, Spanish National Research Council (CSIC), Santander, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Prieto
authors.affiliation: Service of Neurology, University Hospital Marqués de Valdecilla (IDIVAL), University of Cantabria (UC), Santander, Spain; Centro de Investigación en Red de Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Sierra
authors.affiliation: Service of Neurology, University Hospital Marqués de Valdecilla (IDIVAL), University of Cantabria (UC), Santander, Spain; Centro de Investigación en Red de Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Pascual
authors.initials: P
authors.lastname: Sánchez-Juan
authors.affiliation: Service of Neurology, University Hospital Marqués de Valdecilla (IDIVAL), University of Cantabria (UC), Santander, Spain; Centro de Investigación en Red de Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: González-Aramburu
authors.affiliation: Service of Neurology, University Hospital Marqués de Valdecilla (IDIVAL), University of Cantabria (UC), Santander, Spain.
authors.forename: Coro
authors.initials: C
authors.lastname: Sánchez-Quintana
authors.affiliation: Service of Neurology, University Hospital Marqués de Valdecilla (IDIVAL), University of Cantabria (UC), Santander, Spain; Centro de Investigación en Red de Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Berciano
authors.affiliation: Service of Neurology, University Hospital Marqués de Valdecilla (IDIVAL), University of Cantabria (UC), Santander, Spain; Centro de Investigación en Red de Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Onofre
authors.initials: O
authors.lastname: Combarros
authors.affiliation: Institute of Biomedicine and Biotechnology of Cantabria, Spanish National Research Council (CSIC), Santander, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Sainz
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D056726:Genetic Association Studies / Q000379:methods*; D055106:Genome-Wide Association Study; D006579:Heterozygote; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010300:Parkinson Disease / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D017423:Sequence Analysis, RNA
chemical_list: D012333:RNA, Messenger; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases
keywords: Gene expression; LRRK2; Parkinson's disease; Peripheral blood; RNA-seq; Transcriptome