Variants in the Niemann-Pick type C gene NPC1 are not associated with Parkinson's disease.

Aged Female Genetic Association Studies Genetic Variation Humans Intracellular Signaling Peptides and Proteins / genetics Lysosomes / genetics Male Middle Aged Negative Results Niemann-Pick C1 Protein Niemann-Pick Disease, Type C / genetics Parkinson Disease / genetics alpha-Synuclein
Lysosomal genes NPC1 Niemann–Pick disease type C Parkinson's disease

Journal

Neurobiology of aging
ISSN: 1558-1497
Titre abrégé: Neurobiol Aging
Pays: United States
ID NLM: 8100437

Informations de publication

Date de publication:
09 2020
Historique:
received: 04 03 2020
revised: 27 03 2020
accepted: 28 03 2020
pubmed: 7 5 2020
medline: 16 1 2021
entrez: 7 5 2020
Statut: ppublish

Résumé

Biallelic variants in NPC1, a gene coding for a lysosomal transmembrane protein involved in cholesterol trafficking, may cause Niemann-Pick disease type C (NPC). A few cases of NPC1 variant carriers with Parkinson's disease (PD) have been reported. In addition, pathologic studies have demonstrated phosphorylated alpha-synuclein and Lewy pathology in brains of NPC patients. Therefore, we aimed to examine whether NPC1 genetic variants may be associated with PD. Full sequencing of NPC1 was performed in 2657 PD patients and 3647 controls from 3 cohorts, using targeted sequencing with molecular inversion probes. A total of 9 common variants and 126 rare variants were identified across the 3 cohorts. To examine their association with PD, regression models adjusted for age, sex, and origin were performed for common variants, and optimal sequence Kernel association test (SKAT-O) was performed for rare variants. After correction for multiple comparisons, common and rare NPC1 variants were not associated with PD. Our results do not support a link between heterozygous variants in NPC1 and PD.

Identifiants

DOI: 10.1016/j.neurobiolaging.2020.03.021 PMID: 32371106 PMC: PMC7302975
pubmed: 32371106
pii: S0197-4580(20)30112-3
doi: 10.1016/j.neurobiolaging.2020.03.021
pmc: PMC7302975
mid: NIHMS1582681
pii:
doi:

Substances chimiques

Intracellular Signaling Peptides and Proteins 0
NPC1 protein, human 0
Niemann-Pick C1 Protein 0
alpha-Synuclein 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

143.e1-143.e4

Subventions

Organisme : NINDS NIH HHS
ID : K02 NS080915
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000040
Pays : United States
Organisme : CIHR
ID : FDN 154301
Pays : Canada

Informations de copyright

Copyright © 2020 Elsevier Inc. All rights reserved.

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Auteurs

Bouchra Ouled Amar Bencheikh (B)

Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada; Centre de Recherche, Centre Hospitalier de l'Universite de Montreal, Montreal, Quebec, Canada.

Konstantin Senkevich (K)

Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada; Department of Neurology and neurosurgery, McGill University, Montréal, Quebec, Canada.

Uladzislau Rudakou (U)

Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada; Department of Human Genetics, McGill University, Montréal, Quebec, Canada.

Eric Yu (E)

Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada; Department of Human Genetics, McGill University, Montréal, Quebec, Canada.

Kheireddin Mufti (K)

Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada; Department of Human Genetics, McGill University, Montréal, Quebec, Canada.

Jennifer A Ruskey (JA)

Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada; Department of Neurology and neurosurgery, McGill University, Montréal, Quebec, Canada.

Farnaz Asayesh (F)

Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada; Department of Neurology and neurosurgery, McGill University, Montréal, Quebec, Canada.

Sandra B Laurent (SB)

Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada; Department of Neurology and neurosurgery, McGill University, Montréal, Quebec, Canada.

Dan Spiegelman (D)

Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada.

Stanley Fahn (S)

Department of Neurology, College of Physicians and Surgeons, Columbia University Medical Center, New York, NY, USA.

Cheryl Waters (C)

Department of Neurology, College of Physicians and Surgeons, Columbia University Medical Center, New York, NY, USA.

Oury Monchi (O)

Department of Neurology and neurosurgery, McGill University, Montréal, Quebec, Canada; Department of Clinical Neurosciences and Department of Radiology, University of Calgary, Calgary, Alberta, Canada; Hotchkiss Brain Institute, Cumming School of Medicine, Calgary, Alberta, Canada.

Yves Dauvilliers (Y)

Department of Neurology, National Reference Center for Narcolepsy, Sleep Unit, Gui-de-Chauliac Hospital, CHU Montpellier, University of Montpellier, Montpellier, France.

Alberto J Espay (AJ)

Department of Neurology, Gardner Family Center for Parkinson's Disease and Movement Disorders, University of Cincinnati, Cincinnati, OH, USA.

Nicolas Dupré (N)

Division of Neurosciences, CHU de Québec, Université Laval, Quebec City, Quebec, Canada; Department of Medicine, Faculty of Medicine, Université Laval, Québec, Quebec, Canada.

Lior Greenbaum (L)

Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; The Danek Gertner Institute of Human Genetics, Sheba Medical Center, Tel Hashomer, Israel; The Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel Hashomer, Israel.

Sharon Hassin-Baer (S)

Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; The Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel Hashomer, Israel; Department of Neurology, The Movement Disorders Institute, Sheba Medical Center, Tel Hashomer, Israel.

Guy A Rouleau (GA)

Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada; Department of Neurology and neurosurgery, McGill University, Montréal, Quebec, Canada; Department of Human Genetics, McGill University, Montréal, Quebec, Canada.

Roy N Alcalay (RN)

Department of Neurology, College of Physicians and Surgeons, Columbia University Medical Center, New York, NY, USA; Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY, USA.

Edward A Fon (EA)

Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada; Department of Neurology and neurosurgery, McGill University, Montréal, Quebec, Canada.

Ziv Gan-Or (Z)

Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada; Department of Neurology and neurosurgery, McGill University, Montréal, Quebec, Canada; Department of Human Genetics, McGill University, Montréal, Quebec, Canada. Electronic address: ziv.gan-or@mcgill.ca.

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › Variants in the Niemann-Pick type C gene NPC1...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Études d'associations génétiques › Variants in the Niemann-Pick type C gene NPC1...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Variants in the Niemann-Pick type C gene NPC1...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Variants in the Niemann-Pick type C gene NPC1...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Variants in the Niemann-Pick type C gene NPC1...
questionsmedicales.fr › Cellules › Structures cellulaires › Espace intracellulaire › Cytoplasme › Structures cytoplasmiques › Organites › Vésicules cytoplasmiques › Lysosomes › Variants in the Niemann-Pick type C gene NPC1...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › Variants in the Niemann-Pick type C gene NPC1...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Collecte de données › Résultats négatifs › Variants in the Niemann-Pick type C gene NPC1...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines tumorales › Protéines suppresseurs de tumeurs › Récepteurs patched › Protéine NPC1 › Variants in the Niemann-Pick type C gene NPC1...
questionsmedicales.fr › Maladies métaboliques et nutritionnelles › Maladies métaboliques › Erreurs innées du métabolisme › Maladies lysosomiales › Maladies neurologiques de surcharge lysosomiale › Sphingolipidoses › Maladies de Niemann-Pick › Maladie de Niemann-Pick de type C › Variants in the Niemann-Pick type C gene NPC1...
questionsmedicales.fr › Maladies du système nerveux › Maladies neurodégénératives › Maladie de Parkinson › Variants in the Niemann-Pick type C gene NPC1...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines associées à la maladie de Parkinson › alpha-Synucléine › Variants in the Niemann-Pick type C gene NPC1...