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.