Association of a polymorphism in the dopamine-transporter gene with Parkinson's disease.
The presynaptic dopamine transporter in nigral dopaminergic neurons confers susceptibility to the cytotoxic effects of the neurotoxic metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Polymorphisms in the dopamine transporter might influence the susceptibility to such toxins. Therefore, we investigated whether a polymorphic region in the 3'-untranslated region of the dopamine-transporter gene is associated with idiopathic Parkinson's disease (PD). The frequency distribution of the alleles was significantly different between the patients (n = 100) and controls (n = 200, p < 0.05). The rare 11-copy allele was more common in the patients (odds ratio = 10.2, 95% confidence interval - 1.2-87.9, p < 0.025). The susceptibility of some people to PD may be conferred by polymorphisms in the dopamine-transporter gene that could lead to increased cellular accumulation of neurotoxic compounds in dopaminergic neurons.
Le Couteur
D G
DG
University of Queensland, Department of Medicine, Princess Alexandra Hospital, Woolloongabba, Australia.
Leighton
P W
PW
McCann
S J
SJ
Pond
S m
Sm
D017668:Age of Onset; D000368:Aged; D000483:Alleles; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D016001:Confidence Intervals; D004198:Disease Susceptibility; D050483:Dopamine Plasma Membrane Transport Proteins; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D016017:Odds Ratio; D010300:Parkinson Disease / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics* / Q000502:physiology
D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins