A NEW GENETIC VARIANT IN THE SP1 BINDING CIS-ELEMENT OF CHOLECYSTOKININ GENE PROMOTER REGION AND RELATIONSHIP TO ALCOHOLISM

Neuropeptide cholecystokinin (CCK) and the CCK receptors in the centra l nervous system mediate actions on increasing firings, anxiety, and n ociceptions. Furthermore, CCK modulates the release of dopamine and do pamine-related behaviors in the mesolimbic pathway. In our study, gene tic variation in the promoter and coding regions of the prepro-CCK gen e were analyzed among 66 Japanese, 66 American Whites, 54 Chinese, and 41 Colombian natives. Two nucleotide sequence variants were found: a frequent mutation at nucleotide position -45 C to T involved in core s equence of Spl binding cis-element of the promoter region, and a C to T substitution at the 1662 position in intron 2. Analysis for the segr egation study in 10 families of twins confirmed codominant heredity of two alleles. Distribution of genotypes and gene frequencies of 66 con trols and 108 alcoholics in Japan presented that allelic variant T typ e in alcoholics was found in higher frequencies than that of controls, and distribution of these genotypes was significantly different betwe en the both groups.