Common and rare GCH1 variants are associated with Parkinson's disease.
Dopa-responsive dystonia (DRD)
GCH1
GTP cyclohydrolase 1 deficiency
Parkinson disease
Journal
Neurobiology of aging
ISSN: 1558-1497
Titre abrégé: Neurobiol Aging
Pays: United States
ID NLM: 8100437
Informations de publication
Date de publication:
01 2019
01 2019
Historique:
received:
06
06
2018
revised:
07
09
2018
accepted:
07
09
2018
pubmed:
14
10
2018
medline:
20
12
2019
entrez:
14
10
2018
Statut:
ppublish
Résumé
GCH1 encodes the enzyme guanosine triphospahte (GTP) cyclohydrolase 1, essential for dopamine synthesis in nigrostriatal cells, and rare mutations in GCH1 may lead to Dopa-responsive dystonia (DRD). While GCH1 is implicated in genomewide association studies in Parkinson's disease (PD), only a few studies examined the role of rare GCH1 variants in PD, with conflicting results. In the present study, GCH1 and its 5' and 3' untranslated regions were sequenced in 1113 patients with PD and 1111 controls. To examine the association of rare GCH1 variants with PD, burden analysis was performed. Three rare GCH1 variants, which were previously reported to be pathogenic in DRD, were found in five patients with PD and not in controls (sequence Kernel association test, p = 0.024). A common haplotype, tagged by rs841, was associated with a reduced risk for PD (OR = 0.71, 95% CI = 0.61-0.83, p = 1.24 × 10
Identifiants
pubmed: 30314816
pii: S0197-4580(18)30331-2
doi: 10.1016/j.neurobiolaging.2018.09.008
pmc: PMC6251729
mid: NIHMS988338
pii:
doi:
Substances chimiques
GCH1 protein, human
EC 3.5.4.16
GTP Cyclohydrolase
EC 3.5.4.16
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
231.e1-231.e6Subventions
Organisme : NINDS NIH HHS
ID : K02 NS080915
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000040
Pays : United States
Informations de copyright
Copyright © 2018 Elsevier Inc. All rights reserved.
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