Genetic polymorphisms in Parkinson disease subjects with and without hallucinations: an analysis of the cholecystokinin system

Arch Neurol. 2004 Aug;61(8):1280-4. doi: 10.1001/archneur.61.8.1280.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alleles
  • Case-Control Studies
  • Cholecystokinin / genetics*
  • Dopamine Agents / therapeutic use
  • Female
  • Gene Frequency
  • Hallucinations / drug therapy
  • Hallucinations / genetics*
  • Hallucinations / psychology
  • Humans
  • Male
  • Middle Aged
  • Parkinson Disease / drug therapy
  • Parkinson Disease / genetics*
  • Parkinson Disease / psychology
  • Polymorphism, Genetic / genetics*
  • Receptors, Cholecystokinin / genetics*

Substances

  • Dopamine Agents
  • Receptors, Cholecystokinin
  • Cholecystokinin