title: Comparative blood transcriptome analysis in idiopathic and LRRK2 G2019S-associated Parkinson's disease.
abstract: Patients with Parkinson's disease (PD) carrying the G2019S mutation of the LRRK2 gene provide an opportunity of studying in a homogeneous setting the molecular pathways involved in the pathogenesis of common idiopathic forms of PD. However, whether common mechanisms are involved in both conditions in not known. Here, we compared genome-wide gene expression (RNA sequencing) in peripheral blood between PD patients carrying the G2019S mutation of the LRRK2 gene and idiopathic PD cases, to deepen in the understanding of this topic. In addition, we compared the blood transcriptome between 2 cohorts of carriers of the G2019S mutation (symptomatic and asymptomatic) and 2 cohorts of noncarriers (symptomatic and asymptomatic) for detecting transcriptomic changes attributable to the presence of the G2019S mutation. We searched for gene enrichment in Reactome or Kyoto Encyclopedia of Genes and Genomes pathways. We found that despite some overlap, peripheral blood transcriptome differs widely between idiopathic and LRRK2 G2019S-associated PD, with only 4 deregulated pathways shared by both conditions (complement and coagulation cascades, cell adhesion molecules, hematopoietic cell lineage, and extracellular matrix organization). Changes in the blood transcriptome observed in asymptomatic carriers of the mutation included 6 genes known to be associated with PD in genome-wide association studies and also pathways related with immunity. Our findings emphasize the notion that PD is likely a pathogenically heterogeneous condition and suggest the existence of specific mechanisms involved in LRRK2-associated 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: Bioinformatics Service, NUCLEUS, University of Salamanca (USAL), Salamanca, 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 (IBBTEC), 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; D015331:Cohort Studies; D015870:Gene Expression; D020869:Gene Expression Profiling; D055106:Genome-Wide Association Study; D006579:Heterozygote; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010300:Parkinson Disease / Q000097:blood* / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D017423:Sequence Analysis, RNA; D059467:Transcriptome
chemical_list: D012333:RNA, Messenger; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
keywords: Gene expression; LRRK2; Parkinson's disease; Peripheral blood; RNA-seq; Trancriptome