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Variants in the Niemann-Pick type C gene NPC1 are not associated with Parkinson's disease.
Ouled Amar Bencheikh, Bouchra; Senkevich, Konstantin; Rudakou, Uladzislau; Yu, Eric; Mufti, Kheireddin; Ruskey, Jennifer A; Asayesh, Farnaz; Laurent, Sandra B; Spiegelman, Dan; Fahn, Stanley; Waters, Cheryl; Monchi, Oury; Dauvilliers, Yves; Espay, Alberto J; Dupré, Nicolas; Greenbaum, Lior; Hassin-Baer, Sharon; Rouleau, Guy A; Alcalay, Roy N; Fon, Edward A; Gan-Or, Ziv.
  • 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.
  • Senkevich K; Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada; Department of Neurology and neurosurgery, McGill University, Montréal, Quebec, Canada.
  • Rudakou U; Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada; Department of Human Genetics, McGill University, Montréal, Quebec, Canada.
  • Yu E; Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada; Department of Human Genetics, McGill University, Montréal, Quebec, Canada.
  • Mufti K; Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada; Department of Human Genetics, McGill University, Montréal, Quebec, Canada.
  • Ruskey JA; Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada; Department of Neurology and neurosurgery, McGill University, Montréal, Quebec, Canada.
  • Asayesh F; Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada; Department of Neurology and neurosurgery, McGill University, Montréal, Quebec, Canada.
  • Laurent SB; Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada; Department of Neurology and neurosurgery, McGill University, Montréal, Quebec, Canada.
  • Spiegelman D; Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada.
  • Fahn S; Department of Neurology, College of Physicians and Surgeons, Columbia University Medical Center, New York, NY, USA.
  • Waters C; Department of Neurology, College of Physicians and Surgeons, Columbia University Medical Center, New York, NY, USA.
  • 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.
  • Dauvilliers Y; Department of Neurology, National Reference Center for Narcolepsy, Sleep Unit, Gui-de-Chauliac Hospital, CHU Montpellier, University of Montpellier, Montpellier, France.
  • Espay AJ; Department of Neurology, Gardner Family Center for Parkinson's Disease and Movement Disorders, University of Cincinnati, Cincinnati, OH, USA.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • Fon EA; Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada; Department of Neurology and neurosurgery, McGill University, Montréal, Quebec, Canada.
  • 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.
Neurobiol Aging ; 93: 143.e1-143.e4, 2020 09.
Article en En | MEDLINE | ID: mdl-32371106
ABSTRACT
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.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Enfermedad de Parkinson / Variación Genética / Péptidos y Proteínas de Señalización Intracelular / Enfermedad de Niemann-Pick Tipo C / Estudios de Asociación Genética / Resultados Negativos Tipo de estudio: Risk_factors_studies Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Año: 2020 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Search on Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Enfermedad de Parkinson / Variación Genética / Péptidos y Proteínas de Señalización Intracelular / Enfermedad de Niemann-Pick Tipo C / Estudios de Asociación Genética / Resultados Negativos Tipo de estudio: Risk_factors_studies Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Año: 2020 Tipo del documento: Article