Linked polymorphisms (-333G>T and -286A>G) in the promoter region of the CCK-A receptor gene may be associated with schizophrenia

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 201 A > 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 I of the CCKAR gene. In addition to polyrnorphisms 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. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.