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Comparative blood transcriptome analysis in idiopathic and LRRK2 G2019S-associated Parkinson's disease.
Neurobiol Aging. 2016 Feb; 38:214.e1-214.e5.NA

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+Show Affiliations

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.Bioinformatics Service, NUCLEUS, University of Salamanca (USAL), Salamanca, Spain.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.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.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.Service of Neurology, University Hospital Marqués de Valdecilla (IDIVAL), University of Cantabria (UC), Santander, Spain.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.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.Institute of Biomedicine and Biotechnology of Cantabria (IBBTEC), Spanish National Research Council (CSIC), Santander, Spain.

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26675812

Citation

Infante, Jon, et al. "Comparative Blood Transcriptome Analysis in Idiopathic and LRRK2 G2019S-associated Parkinson's Disease." Neurobiology of Aging, vol. 38, 2016, pp. 214.e1-214.e5.
Infante J, Prieto C, Sierra M, et al. Comparative blood transcriptome analysis in idiopathic and LRRK2 G2019S-associated Parkinson's disease. Neurobiol Aging. 2016;38:214.e1-214.e5.
Infante, J., Prieto, C., Sierra, M., Sánchez-Juan, P., González-Aramburu, I., Sánchez-Quintana, C., Berciano, J., Combarros, O., & Sainz, J. (2016). Comparative blood transcriptome analysis in idiopathic and LRRK2 G2019S-associated Parkinson's disease. Neurobiology of Aging, 38, e1-e5. https://doi.org/10.1016/j.neurobiolaging.2015.10.026
Infante J, et al. Comparative Blood Transcriptome Analysis in Idiopathic and LRRK2 G2019S-associated Parkinson's Disease. Neurobiol Aging. 2016;38:214.e1-214.e5. PubMed PMID: 26675812.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comparative blood transcriptome analysis in idiopathic and LRRK2 G2019S-associated Parkinson's disease. AU - Infante,Jon, AU - Prieto,Carlos, AU - Sierra,María, AU - Sánchez-Juan,Pascual, AU - González-Aramburu,Isabel, AU - Sánchez-Quintana,Coro, AU - Berciano,José, AU - Combarros,Onofre, AU - Sainz,Jesús, Y1 - 2015/10/31/ PY - 2015/06/07/received PY - 2015/09/16/revised PY - 2015/10/27/accepted PY - 2015/12/18/entrez PY - 2015/12/18/pubmed PY - 2016/12/15/medline KW - Gene expression KW - LRRK2 KW - Parkinson's disease KW - Peripheral blood KW - RNA-seq KW - Trancriptome SP - 214.e1 EP - 214.e5 JF - Neurobiology of aging JO - Neurobiol Aging VL - 38 N2 - 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. SN - 1558-1497 UR - https://www.unboundmedicine.com/medline/citation/26675812/Comparative_blood_transcriptome_analysis_in_idiopathic_and_LRRK2_G2019S_associated_Parkinson's_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0197-4580(15)00538-2 DB - PRIME DP - Unbound Medicine ER -