Cg. Goetz et al., Genetic variation analysis in Parkinson disease patients with and without hallucinations - Case-control study, ARCH NEUROL, 58(2), 2001, pp. 209-213
Background: Visual hallucinations in Parkinson disease (PD) occur in approx
imately one third of patients treated long-term with dopaminergic medicatio
ns. In Alzheimer disease, hallucinations and psychosis have been linked to
increased representations of B2/B2 homozyogotes for the dopamine receptor g
ene 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 pe
rformed. Another study linked the apolipoprotein E4 (APOE4) allele to hallu
cinations in PD.
Objective: To determine whether the frequency of dopamine receptor genetic
variants and APOE alleles in patients with PD with and without chronic visu
al hallucinations resembles the pattern previously documented in patients w
ith Alzheimer disease.
Methods: We conducted a case-control study of 44 patients with PD and chron
ic hallucinations and 44 patients with PD who had never hallucinated. Cases
and controls were matched for current age and medications. DNA was isolate
d from blood samples and assayed for DRD1, DRD2, DRD3, DRD4, and APOE polym
orphisms. Receptor polymorphisms were genotyped by polymerase chain reactio
n. Genotypes in hallucinators and non-hallucinators were compared using Man
tel-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 d
istribution 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 gen
otypes or frequencies. For APOE, 12 cases and 12 controls carried E4 allele
s (P > .99).
Conclusions: With careful case-control matching, visual hallucinations in P
D are not associated with the pattern seen for patients with Alzheimer dise
ase and visual hallucinations. Furthermore, there was no association betwee
n 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 DRD
3 allele 2 may merit further study.