Back to Search
Start Over
A functional polymorphism in the parkin gene promoter affects the age of onset of Parkinson's disease
- Source :
- Neuroscience Letters. 414:170-173
- Publication Year :
- 2007
- Publisher :
- Elsevier BV, 2007.
-
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.
- Subjects :
- Genetic Markers
Male
medicine.medical_specialty
Parkinson's disease
Genotype
Ubiquitin-Protein Ligases
DNA Mutational Analysis
Down-Regulation
Bioinformatics
Gastroenterology
Parkin
Gene Frequency
Polymorphism (computer science)
Internal medicine
medicine
Humans
Genetic Predisposition to Disease
Genetic Testing
Age of Onset
Allele
Promoter Regions, Genetic
Allele frequency
Survival analysis
Aged
Polymorphism, Genetic
business.industry
General Neuroscience
Brain
Parkinson Disease
Middle Aged
medicine.disease
Gene Expression Regulation
Mutation
Female
Age of onset
business
Subjects
Details
- ISSN :
- 03043940
- Volume :
- 414
- Database :
- OpenAIRE
- Journal :
- Neuroscience Letters
- Accession number :
- edsair.doi.dedup.....8326fc482b6a5e99379c731353a3f570