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Novel polymorphisms of the human cholecystokinin a receptor gene: An association analysis with schizophrenia

โœ Scribed by Tachikawa, Hirokazu; Harada, Shoji; Kawanishi, Yoichi; Okubo, Takehito; Shiraishi, Hiroyasu


Publisher
John Wiley and Sons
Year
2000
Tongue
English
Weight
15 KB
Volume
96
Category
Article
ISSN
0148-7299
DOI
10.1002/(sici)1096-8628(20000403)96:2<141::aid-ajmg3>3.0.co;2-r

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โœฆ Synopsis


The cholecystokinin A receptor (CCK-AR) modulates CCK-stimulated dopamine release in the posterior nucleus accumbens, and its gene is mapped to 4p15.2-15.1 with the dopamine receptor 5 (DR5) gene. We speculated that alterations in the CCK-AR lead to an increase in dopamine release, which may in turn constitute a predisposition in schizophrenia. We investigated genetic variations in the promoter region and the coding region of the CCK-AR gene. An association analysis was conducted between 83 unrelated schizophrenic patients and 80 healthy controls. Novel polymorphisms (201Aโ†’G, 246Gโ†’A in the promoter region, 1260Tโ†’A, 1266Tโ†’C in intron 1 within the 3 mRNA splice acceptor site consensus sequence, and Leu306Leu in exon 5) were found in addition to the variants (608Gโ†’A in intron 1, 3849Cโ†’T [Ile296Ile] in exon 5) reported previously. Significant differences were found in the allele frequencies of the 201Aโ†’G nucleotide substitution in the promoter region between patients and controls (P = 0.0181, odds ratio: 1.972, after Bonferroni correction: P = 0.0543). These differences were also found between the patients with paranoid type and controls (P = 0.0274, odds ratio = 3.667, after Bonferroni correction: P = 0.0822). Our analyses suggest that the 201A allele frequency was higher in the schizophrenic group, especially in the paranoid type, than in the control group at a rate that was not quite significant after Bonferroni correction.


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