Genetic variations in the 5-untranslated region and the coding region of the CCK-B receptor (CCK-BR) gene were investigated in healthy controls. Novel variants (-215 CโA, Leu37Phe, Arg319Glu) were found in addition to the mutations (Val125Iso, His207His, Arg215His, 2491 CโA) reported previously. In
Novel polymorphisms of the human cholecystokinin a receptor gene: An association analysis with schizophrenia
โ 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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โฆ 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 (201AโG, 246GโA in the promoter region, 1260TโA, 1266TโC in intron 1 within the 3 mRNA splice acceptor site consensus sequence, and Leu306Leu in exon 5) were found in addition to the variants (608GโA in intron 1, 3849CโT [Ile296Ile] in exon 5) reported previously. Significant differences were found in the allele frequencies of the 201AโG 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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