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Genetic Variation Analysis in Parkinson Disease Patients With and Without Hallucinations
Case-Control Study
Christopher G. Goetz, MD;
Paul F. Burke, MD;
Sue Leurgans, PhD;
Elizabeth Berry-Kravis, MD;
Lucy M. Blasucci, RN;
Rema Raman, MS;
Lili Zhou, MD
Arch Neurol. 2001;58:209-213.
Background Visual hallucinations in Parkinson disease (PD) occur in approximately
one third of patients treated long-term with dopaminergic medications. In
Alzheimer disease, hallucinations and psychosis have been linked to increased
representations of B2/B2 homozyogotes for the dopamine receptor gene DRD1 and 1/1 or 2/2 homozygotes for DRD3. In addition, a previous study of PD patients with and without
hallucinations did not show differences in D2 and D3 polymorphisms, although
careful case-control matching was not performed. Another study linked the
apolipoprotein E4 (APOE4) allele to hallucinations
in PD.
Objective To determine whether the frequency of dopamine receptor genetic variants
and APOE alleles in patients with PD with and without
chronic visual hallucinations resembles the pattern previously documented
in patients with Alzheimer disease.
Methods We conducted a case-control study of 44 patients with PD and chronic
hallucinations and 44 patients with PD who had never hallucinated. Cases and
controls were matched for current age and medications. DNA was isolated from
blood samples and assayed for DRD1, DRD2, DRD3, DRD4,
and APOE polymorphisms. Receptor polymorphisms were
genotyped by polymerase chain reaction. Genotypes in hallucinators and nonhallucinators
were compared using Mantel-Haenszel tests stratified by pair, and allele frequencies
were compared using Wilcoxon signed rank tests within pairs.
Results Neither D1 receptor genotypes (P = .37) nor
allele frequencies (P = .38) differed, and there
was no predominance of B2/B2 homozygotes in the hallucinators. For D3, there
was a higher frequency of allele 2 (P = .047), but
there was no significant difference between frequencies of homozygotes vs
heterozygotes (P = .39) as reported in Alzheimer
disease. D4 receptor distribution of long and short alleles did not differ
between the 2 patient groups, and there were too few C
alleles (3 of 86) to compare D2 allele genotypes or frequencies. For APOE, 12 cases and 12 controls carried E4 alleles (P>.99).
Conclusions With careful case-control matching, visual hallucinations in PD are
not associated with the pattern seen for patients with Alzheimer disease and
visual hallucinations. Furthermore, there was no association between hallucinations
and APOE. Similar methods using larger sample sizes
might be adapted to test whether specific dopaminergic receptor genetic variants
are associated with visual hallucinations in PD. Based on our data, the DRD3 allele 2 may merit further study.
From the Departments of Neurological Sciences (Drs Goetz, Burke, Leurgans,
and Berry-Kravis and Ms Blasucci), Pharmacology (Dr Goetz), Preventive Medicine
(Dr Leurgans and Ms Raman), and Pediatrics (Drs Berry-Kravis and Zhou), Rush
University/Rush-Presbyterian-St Luke's Medical Center, Chicago, Ill.
Corresponding author: Christopher G. Goetz, MD, Department of Neurological
Sciences, Rush
University/Rush-Presbyterian-St Luke's Medical Center, 1725
W Harrison St, Chicago, IL 60612.
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