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An Analysis of the Cholecystokinin System

Jennifer G. Goldman, MD; Christopher G. Goetz, MD; Elizabeth Berry-Kravis, MD; Sue Leurgans, PhD; Lili Zhou, MD

Arch Neurol. 2004;61:1280-1284.

Background  Hallucinations in patients with Parkinson disease (PD), occurring in about one third of those receiving long-term dopaminergic therapy, contribute to morbidity and mortality. In matched Chinese PD subjects with and without hallucinations, the presence of the –45 C/T locus in the cholecystokinin (CCK) gene, particularly when combined with the CCK receptor, CCKAR (cholecystokinin A receptor), C polymorphism, was associated with increased hallucination risk. Because CCK gene polymorphisms vary across ethnic groups, the presence of similar associations in white PD subjects merits investigation.

Objective  To determine whether polymorphisms of CCK and CCK receptor genes are associated with hallucinations in white PD subjects.

Design  Case-control study of PD subjects with and without chronic hallucinations matched for age and dopaminergic medication. Genomic DNA was analyzed for CCK, CCKAR, and CCKBR (cholecystokinin B receptor) polymorphisms by polymerase chain reaction. Genotype distributions and allele frequencies were compared between groups and in matched pairs.

Results  Comparing matched pairs, we found more frequent representation of the CCK T allele in hallucinating PD subjects, although this finding was not statistically significant (P = .06). Of 5 cases with both CCK T and CCKAR C alleles, 4 were hallucinators. Cases and controls did not differ in CCKAR or CCKBR polymorphisms.

Conclusions  Our study supports a previous association of hallucinations in PD subjects with the CCK T allele and the combined CCK T and CCKAR C allele, suggesting that the CCK system may influence the development of hallucinations in PD subjects. The lower representation of the T allele in our white sample limited our statistical power. Further assessment of the T allele as a risk factor for hallucinations would include longitudinal study of nonhallucinators to detect the evolution of hallucinations relative to T allele frequency.

Author Affiliations: Departments of Neurological Sciences (Drs Goldman, Goetz, Berry-Kravis, and Leurgans), Pharmacology (Dr Goetz), Pediatrics (Drs Berry-Kravis and Zhou), and Preventive Medicine (Dr Leurgans), Rush-Presbyterian-St Luke’s Medical Center, Chicago, Ill.