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BACKGROUND: Levodopa induced dyskinesias (LID) are a common problem which ultimately limit the effective treatment of patients with Parkinson's disease (PD). There is accumulating evidence that LID develop due to abnormal synaptic plasticity, which is in turn influenced by the release of brain derived neurotrophic factor (BDNF). METHODS: The influence of a common functional polymorphism of the BDNF gene on the risk of developing dyskinesias in a large cohort of patients with PD (n = 315), who were independently and variably treated with levodopa and/or other dopaminergic treatments, was investigated. RESULTS: Patients with the met allele of BDNF, associated with lower activity dependent secretion of BDNF, were at significantly higher risk of developing dyskinesias earlier in the course of treatment with dopaminergic agents (hazard ratio for each additional met allele 2.12, p = 0.001), which persisted following adjustment for potential confounding variables. CONCLUSION: This functional polymorphism may help predict which individuals are most at risk of LID and is consistent with the known actions of BDNF on synaptic plasticity in the striatum.

Original publication

DOI

10.1136/jnnp.2008.154294

Type

Journal article

Journal

J Neurol Neurosurg Psychiatry

Publication Date

02/2009

Volume

80

Pages

141 - 144

Keywords

Adult, Aged, Alleles, Antiparkinson Agents, Brain-Derived Neurotrophic Factor, Corpus Striatum, Dyskinesia, Drug-Induced, Female, Gene Expression, Genotype, Humans, Levodopa, Male, Middle Aged, Neuronal Plasticity, Parkinson Disease, Polymorphism, Genetic, Receptor, trkB, Risk Factors, Synapses, Time Factors