Goldman Jennifer G, Goetz Christopher G, Berry-Kravis Elizabeth, Leurgans Sue, Zhou Lili
Department of Neurological Sciences, Rush-Presbyterian-St Luke's Medical Center, Chicago, Ill. 60612, USA.
Arch Neurol. 2004 Aug;61(8):1280-4. doi: 10.1001/archneur.61.8.1280.
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.
To determine whether polymorphisms of CCK and CCK receptor genes are associated with hallucinations in white PD subjects.
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.
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.
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.
帕金森病（PD）患者出现幻觉的情况在接受长期多巴胺能治疗的患者中约占三分之一，会导致发病和死亡。在匹配的有幻觉和无幻觉的中国PD患者中，胆囊收缩素（CCK）基因中-45 C/T位点的存在，特别是与CCK受体CCKAR（胆囊收缩素A受体）C多态性相结合时，与幻觉风险增加相关。由于CCK基因多态性在不同种族群体中存在差异，因此在白人PD患者中是否存在类似关联值得研究。
确定CCK和CCK受体基因多态性是否与白人PD患者的幻觉有关。
对有和无慢性幻觉的PD患者进行病例对照研究，匹配年龄和多巴胺能药物治疗情况。通过聚合酶链反应分析基因组DNA的CCK、CCKAR和CCKBR（胆囊收缩素B受体）多态性。比较组间和匹配对中的基因型分布和等位基因频率。
比较匹配对时，我们发现幻觉PD患者中CCK T等位基因的出现频率更高，尽管这一发现无统计学意义（P = 0.06）。在5例同时具有CCK T和CCKAR C等位基因的患者中，4例有幻觉。病例组和对照组在CCKAR或CCKBR多态性方面无差异。
我们的研究支持先前关于PD患者幻觉与CCK T等位基因以及CCK T和CCKAR C等位基因组合相关的关联，表明CCK系统可能影响PD患者幻觉的发生。我们白人样本中T等位基因的出现频率较低，限制了我们的统计效力。将T等位基因作为幻觉风险因素的进一步评估将包括对无幻觉者进行纵向研究，以检测相对于T等位基因频率的幻觉演变情况。
