Variants in the Niemann-Pick type C gene NPC1 are not associated with Parkinson’s disease,Neurobiology of Aging

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Variants in the Niemann-Pick type C gene NPC1 are not associated with Parkinson’s disease
Neurobiology of Aging ( IF 4.2 ) Pub Date : 2020-09-01 , DOI: 10.1016/j.neurobiolaging.2020.03.021
Bouchra Ouled Amar Bencheikh ₁ , Konstantin Senkevich ₂ , Uladzislau Rudakou ₃ , Eric Yu ₃ , Kheireddin Mufti ₃ , Jennifer A Ruskey ₂ , Farnaz Asayesh ₂ , Sandra B Laurent ₂ , Dan Spiegelman ₄ , Stanley Fahn ₅ , Cheryl Waters ₅ , Oury Monchi ₆ , Yves Dauvilliers ₇ , Alberto J Espay ₈ , Nicolas Dupré ₉ , Lior Greenbaum ₁₀ , Sharon Hassin-Baer ₁₁ , Guy A Rouleau ₁₂ , Roy N Alcalay ₁₃ , Edward A Fon ₂ , Ziv Gan-Or ₁₂

Affiliation

Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada; Centre de Recherche, Centre Hospitalier de l'Universite de Montreal, Montreal, Quebec, Canada.
Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada; Department of Neurology and neurosurgery, McGill University, Montréal, Quebec, Canada.
Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada; Department of Human Genetics, McGill University, Montréal, Quebec, Canada.
Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada.
Department of Neurology, College of Physicians and Surgeons, Columbia University Medical Center, New York, NY, USA.
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.
Department of Neurology, National Reference Center for Narcolepsy, Sleep Unit, Gui-de-Chauliac Hospital, CHU Montpellier, University of Montpellier, Montpellier, France.
Department of Neurology, Gardner Family Center for Parkinson's Disease and Movement Disorders, University of Cincinnati, Cincinnati, OH, USA.
Division of Neurosciences, CHU de Québec, Université Laval, Quebec City, Quebec, Canada; Department of Medicine, Faculty of Medicine, Université Laval, Québec, Quebec, Canada.
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.
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.
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.
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.

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.

更新日期：2020-09-01

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