Functional association of the parkin gene promoter with idiopathic Parkinson's disease.
Loss-of-function mutations in the parkin gene were first identified in autosomal recessive juvenile parkinsonism (AR-JP). Subsequently, parkin mutations were found in many early-onset patients with Parkinson's disease (PD) (<45 years at onset). We hypothesized that parkin gene expression also may contribute to the age-associated risk of idiopathic PD (>50 years at onset). Two single-nucleotide polymorphisms within the parkin core promoter have been identified and assessed. We show one of the variants, -258 T/G, is located in a region of DNA that binds nuclear protein from human substantia nigra in vitro and functionally affects gene transcription. Furthermore, the -258 T/G polymorphism is genetically associated with idiopathic PD, as assessed in a large population-based series of cases and controls. Our results further implicate the parkin gene in the development of Parkinson's disease.
Duke Scholars
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- Ubiquitin-Protein Ligases
- Transfection
- Substantia Nigra
- Promoter Regions, Genetic
- Polymorphism, Single Nucleotide
- Parkinson Disease
- Nuclear Proteins
- Nerve Tissue Proteins
- Mutation
- Molecular Sequence Data
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Ubiquitin-Protein Ligases
- Transfection
- Substantia Nigra
- Promoter Regions, Genetic
- Polymorphism, Single Nucleotide
- Parkinson Disease
- Nuclear Proteins
- Nerve Tissue Proteins
- Mutation
- Molecular Sequence Data