A functional polymorphism in the parkin gene promoter affects the age of onset of Parkinson's disease

Neurosci Lett. 2007 Mar 6;414(2):170-3. doi: 10.1016/j.neulet.2006.12.051. Epub 2007 Jan 7.

Abstract

Mutations in the parkin gene are the major cause of autosomal recessive early-onset forms of Parkinson's disease (PD). As reduced parkin expression might also affect the clinical course of idiopathic PD we investigated the effect of a low expressing allele in the parkin promoter region on the age at disease onset (AAO). Patients with PD (n=175) fulfilling standard diagnostic criteria were recruited by experienced neurologists at two movement disorders clinics in Sydney and Brisbane, Australia. DNA was extracted from whole blood and the -258 T/G polymorphism genotyped using PCR/RFLP. AAO effects were analysed using univariate ANOVA, binomial logistic regression modelling and Kaplan-Meier survival analysis. Subjects with the GG genotype (n=10, mean AAO=46.2+/-11.5 (S.D.) years) had a significantly lower mean AAO compared to the common TT genotype (n=104, mean AAO=56.1+/-12.7, p=0.02). There was no difference in mean AAO between the TT and TG individuals (n=61, mean AAO=55.3+/-11.6). Stratifying the sample by median AAO (55 years) revealed that the GG genotype was over-represented in the early-onset group (n=9, OR=18.6, 95% CI=1.41-245.3, p=0.03). We speculate that reduced expression of normal parkin protein may result in an early manifestation of PD symptoms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age of Onset
  • Aged
  • Brain / metabolism*
  • Brain / physiopathology
  • DNA Mutational Analysis
  • Down-Regulation / genetics
  • Female
  • Gene Expression Regulation / genetics
  • Gene Frequency
  • Genetic Markers / genetics
  • Genetic Predisposition to Disease / genetics*
  • Genetic Testing
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Mutation / genetics
  • Parkinson Disease / epidemiology
  • Parkinson Disease / genetics*
  • Parkinson Disease / physiopathology
  • Polymorphism, Genetic / genetics*
  • Promoter Regions, Genetic / genetics*
  • Ubiquitin-Protein Ligases / genetics*

Substances

  • Genetic Markers
  • Ubiquitin-Protein Ligases
  • parkin protein