Association between polymorphism of the cholecystokinin gene and idiopathic Parkinson's disease.
Parkinson's disease (PD) is characterized by major alterations of neurotransmitter activity due to damage of the substantia nigra. Changes in neuropeptide concentration within the basal ganglia may play an important role in the putative dopaminergic-peptidergic interactions associated with the disease. Cholecystokinin (CCK) modulates the release of dopamine in the mesolimbic pathway and affects dopamine-related behavior. We analyzed genetic variations in the CCK gene, in both the coding and promoter region, in order to investigate the role of polymorphism in idiopathic PD. Four polymorphic sites of the CCK gene (-196G/A, -45C/T, 1270C/G, 6662C/T) were found in PD patients and controls. Complete linkage disequilibrium was observed between the -45 locus and the 1270 locus, and also a possible linkage disequilibrium was found between the -45 and -196 loci. A significant difference was found in the distributions of three identified genotypes at the -45 locus between 116 PD patients and 95 age-matched control subjects (chi2 = 7.95, p = 0.018, Bonferroni correction; p = 0.054). In addition, a significant difference was obtained amongst the three genotypic groups at the -45 locus when compared between PD patients who experienced hallucinations (n = 23) and those (n = 93) who did not (chi2 = 8.08, p = 0.018, Bonferroni correction, p = 0.126). Our data suggested that mutations at the -45 locus in the promoter region of the CCK gene may influence vulnerability to hallucinations in PD patients treated with L-dopa.
Fujii
C
C
Department of Environmental Ecosystem, Graduate School of Medicine, University of Tsukuba, Ibaraki, Japan. okeihc@med.keio.ac.jp
Harada
S
S
Ohkoshi
N
N
Hayashi
A
A
Yoshizawa
K
K
Ishizuka
C
C
Nakamura
T
T
D017668:Age of Onset; D000368:Aged; D002766:Cholecystokinin / Q000235:genetics*; D004252:DNA Mutational Analysis; D003627:Data Interpretation, Statistical; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D010300:Parkinson Disease / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D011401:Promoter Regions, Genetic
D002766:Cholecystokinin