title: Linked polymorphisms (-333G>T and -286A>G) in the promoter region of the CCK-A receptor gene may be associated with schizophrenia.
abstract: Cholecystokinin A receptors (CCKAR) modulate CCK-stimulated dopamine release, and mutations in the CCKAR gene may predispose affected individuals to schizophrenia. Our previous study suggested that -286A>G polymorphism (previously named 201A>G) in the CCKAR gene promoter is associated with schizophrenia. In the present study, we carried out a further investigation of the promoter and intron 1 of the CCKAR gene. In addition to polymorphisms reported previously (-333G>T, -286A>G, -241G>A, 773A>T, and 779T>C), two novel polymorphisms (-388(GT)(8)>(GT)(9) and -85C>G) were identified. These polymorphisms were in a linkage disequilibrium. Association analyses between schizophrenic patients and controls revealed that the frequencies of the A allele and AA genotype at the -286 loci, as well as the frequency of the GG genotype at the -333 loci, were significantly higher in patients than in controls. Furthermore, patients with paranoid type schizophrenia, auditory hallucinations, or a positive family history had a significantly higher frequency of the -286A allele than the control group. The results supported our previous data, and suggest the possible involvement of the -333G>T and the -286A>G polymorphisms in the promoter region of the CCKAR gene in the predisposition to schizophrenia.
authors.affiliation: Department of Psychiatry, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, 305-8575, Ibaraki, Japan. praecox@mail1.accsnet.ne.jp
authors.forename: H
authors.initials: H
authors.lastname: Tachikawa
authors.forename: S
authors.initials: S
authors.lastname: Harada
authors.forename: Y
authors.initials: Y
authors.lastname: Kawanishi
authors.forename: T
authors.initials: T
authors.lastname: Okubo
authors.forename: T
authors.initials: T
authors.lastname: Suzuki
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D006580:Genetic Carrier Screening; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006212:Hallucinations / Q000175:diagnosis / Q000235:genetics; D006801:Humans; D007438:Introns; D015810:Linkage Disequilibrium / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011569:Psychiatric Status Rating Scales; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin / Q000235:genetics*; D012559:Schizophrenia / Q000175:diagnosis / Q000235:genetics*; D012563:Schizophrenia, Paranoid / Q000175:diagnosis / Q000235:genetics
chemical_list: D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin