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  • Title: Genetic polymorphisms in Parkinson disease subjects with and without hallucinations: an analysis of the cholecystokinin system.
    Author: Goldman JG, Goetz CG, Berry-Kravis E, Leurgans S, Zhou L.
    Journal: Arch Neurol; 2004 Aug; 61(8):1280-4. PubMed ID: 15313848.
    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.
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