LRRK2 p.M1646T is associated with glucocerebrosidase activity and with Parkinson's disease.
GBA
Glucocerebrosidase
LRRK2
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:
07 2021
07 2021
Historique:
received:
07
10
2020
revised:
07
02
2021
accepted:
23
02
2021
pubmed:
31
3
2021
medline:
24
12
2021
entrez:
30
3
2021
Statut:
ppublish
Résumé
The LRRK2 p.G2019S Parkinson's disease (PD) variant is associated with elevated glucocerebrosidase (GCase) activity in peripheral blood. We aimed to evaluate the association of other LRRK2 variants with PD and its association with GCase activity. LRRK2 and GBA were fully sequenced in 1123 PD patients and 576 controls from the Columbia and PPMI cohorts, in which GCase activity was measured in dried blood spots by liquid chromatography-tandem mass spectrometry. LRRK2 p.M1646T was associated with increased GCase activity in the Columbia University cohort (β = 1.58, p = 0.0003), and increased but not significantly in the PPMI cohort (β = 0.29, p = 0.58). p.M1646T was associated with PD (odds ratio = 1.18, 95% confidence interval = 1.09-1.28, p = 7.33E-05) in 56,306 PD patients and proxy-cases, and 1.4 million controls. Our results suggest that the p.M1646T variant is associated with risk of PD with a small effect and with increased GCase activity in peripheral blood.
Identifiants
pubmed: 33781610
pii: S0197-4580(21)00073-7
doi: 10.1016/j.neurobiolaging.2021.02.018
pmc: PMC8178224
mid: NIHMS1688406
pii:
doi:
Substances chimiques
LRRK2 protein, human
EC 2.7.11.1
Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
EC 2.7.11.1
Glucosylceramidase
EC 3.2.1.45
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
142.e1-142.e5Subventions
Organisme : NINDS NIH HHS
ID : K02 NS080915
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000040
Pays : United States
Informations de copyright
Copyright © 2021 Elsevier Inc. All rights reserved.
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