Functional association of the parkin gene promoter with idiopathic Parkinson's disease

Andrew B. West, Demetrius Maraganore, Julia Crook, Tim Lesnick, Paul J. Lockhart, Kristen M. Wilkes, Gregory Kapatos, John A. Hardy, Matt J. Farrer

Research output: Contribution to journalArticlepeer-review

104 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)2787-2792
Number of pages6
JournalHuman molecular genetics
Issue number22
StatePublished - Oct 15 2002

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)


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