Transcriptional activities of cholecystokinin promoter haplotypes and their relevance to panic disorder susceptibility

We previously identified a polymorphic compound short tandem repeat (STR) in the 5'-regulatory region of the cholecystokinin (CCK) gene, and showed that when the STRs were classified into three groups based on length and linkage disequilibrium behavior with neighboring variants, the medium class allele was significantly associated with panic disorder. The present study examined the transcriptional activity of the CCK promoter construct containing the STR and downstream -188A/G variation. The STRs acted as transcriptional repressors with a similar potency among the three classes, but the long (L) class STR exhibited a synergistic effect on decreasing promoter activity when combined with -1886. The haplotype composed of the L class of STR and -1886 was significantly less frequent in panic disorder (P = 0.0032; odds ratio, 95% confidence interval = 0.06, 0.01-0.69). These results suggest that the L-(-188G) haplotype may act as a protective factor against panic by reducing the expression of anxiogenic CCK. (C) 2003 Wiley-Liss, Inc.