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

Greg Sutherland, George Mellick, Carolyn Sue, Daniel K Y Chan, Dominic Rowe, Peter Silburn, Glenda Halliday*

*Corresponding author for this work

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)170-173
Number of pages4
JournalNeuroscience Letters
Volume414
Issue number2
DOIs
Publication statusPublished - 6 Mar 2007
Externally publishedYes

Keywords

  • Genotype
  • Onset
  • Parkin
  • Parkinson's disease

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