A functional polymorphism in the parkin gene promoter affects the age of onset of Parkinson's disease
MetadataShow full item record
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.