Dopamine transporter gene polymorphism, spect imaging, and levodopa response in patients with Parkinson disease.
OBJECTIVE
To assess the potential association between dopamine transporter (DAT) genotype, single photon emission CT (SPECT) measures using [123I]-N-omega-fluoropropyl-2beta-carbomethoxy-3beta-(4-iodophenyl)nortropane ([123I]-FP-CIT) of striatal dopaminergic function, and oral levodopa response pattern in a cohort of patients with Parkinson disease.


METHODS
Thirty-six patients at different disease stages enrolled in the study. Each patient was examined by [123I]-FP-CIT SPECT and a standardized oral levodopa test on 2 separate days in a randomized order within 3 weeks. The main outcome variables were the specific-to-nonspecific tracer uptake ratio in the contralateral putamen for SPECT analysis; latency, duration, and magnitude of the motor effect; and presence of dyskinesias for the levodopa test. The variable number of tandem repeat (VNTR) polymorphisms of the gene coding for DAT were detected for each patient by standard methods.


RESULTS
Contralateral putamen [123I]-FP-CIT uptake ratios were similar in the patients carrying the 9-copy allele (n=20) of the DAT VNTR compared with 10-repeat homozygotes (n=16). No significant difference was found in levodopa main outcome variables and dyskinesia incidence between the two groups of patients stratified by DAT VNTR polymorphism.


CONCLUSIONS
The study did not identify clinically relevant in vivo DAT neurochemical function phenotypes or levodopa response patterns associated with the DAT polymorphism.
Contin
Manuela
M
Neurology Clinic, Department of Neurological Sciences, University of Bologna, Italy. contin@neuro.unibo.it
Martinelli
Paolo
P
Mochi
Mirella
M
Albani
Fiorenzo
F
Riva
Roberto
R
Scaglione
Cesa
C
Dondi
Maurizio
M
Fanti
Stefano
S
Pettinato
Cinzia
C
Baruzzi
Agostino
A
D000368:Aged; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D050483:Dopamine Plasma Membrane Transport Proteins; D005260:Female; D007839:Functional Laterality / Q000502:physiology; D006801:Humans; D007457:Iodine Radioisotopes; D007980:Levodopa / Q000627:therapeutic use*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins / Q000235:genetics*; D008875:Middle Aged; D009043:Motor Activity / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000235:genetics; D011110:Polymorphism, Genetic; D011699:Putamen / Q000000981:diagnostic imaging; D011930:Reaction Time / Q000187:drug effects; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods; D014326:Tropanes
D000978:Antiparkinson Agents; D050483:Dopamine Plasma Membrane Transport Proteins; D007457:Iodine Radioisotopes; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493214:SLC6A3 protein, human; D014326:Tropanes; C087552:2-carbomethoxy-8-(3-fluoropropyl)-3-(4-iodophenyl)tropane; D007980:Levodopa