BDNF val66met influences time to onset of levodopa induced dyskinesia in Parkinson's disease.
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.


CONCLUSIONS
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.
Foltynie
T
T
Cambridge Centre for Brain Repair, Cambridge, UK. T.Foltynie@ion.ucl.ac.uk
Cheeran
B
B
Williams-Gray
C H
CH
Edwards
M J
MJ
Schneider
S A
SA
Weinberger
D
D
Rothwell
J C
JC
Barker
R A
RA
Bhatia
K P
KP
D000328:Adult; D000368:Aged; D000483:Alleles; D000978:Antiparkinson Agents / Q000009:adverse effects*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D003342:Corpus Striatum / Q000378:metabolism; D004409:Dyskinesia, Drug-Induced / Q000209:etiology*; D005260:Female; D015870:Gene Expression / Q000235:genetics; D005838:Genotype; D006801:Humans; D007980:Levodopa / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009473:Neuronal Plasticity / Q000502:physiology; D010300:Parkinson Disease / Q000188:drug therapy* / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D020813:Receptor, trkB / Q000235:genetics; D012307:Risk Factors; D013569:Synapses / Q000378:metabolism; D013997:Time Factors
D000978:Antiparkinson Agents; D019208:Brain-Derived Neurotrophic Factor; D007980:Levodopa; D020813:Receptor, trkB