No association or linkage between polymorphisms in the genes encoding cholecystokinin and the cholecystokinin B receptor and panic disorder

Growing animal data implicate cholecystokinin in the regulation of anxiety, while human clinical research confirms the role of cholecystokinin in the provocation of panic attacks. Anti-panic medications suppress the ability o f cholecystokinin to induce panic attacks, and may alter the expression of the cholecystokinin gene. Thus, there is increased interest in understandin g the molecular genetic component of these observations. Recent association studies using persons with panic disorder described some association betwe en polymorphisms in the genes encoding cholecystokinin and the cholecystoki nin B-receptor and panic disorder. In this study, we used a family-based de sign, employing 596 individuals in 70 panic disorder pedigrees, as well as 77 haplotype relative risk 'triads', Subjects were genotyped for two polymo rphisms: the polymorphic microsatellite marker in the CCK-BR locus using PC R-based genotyping and at a single nucleotide polymorphism in the CCK promo ter using a fluorescence polarization detection assay, and the data were an alyzed for genetic association and linkage. Employing a variety of diagnost ic and genetic models, linkage analysis produced no significant lod scores at either locus. Family-based tests of association, the haplotype-based hap lotype relative risk statistic and the transmission disequilibrium test, we re likewise non-significant. The results reported here provide little suppo rt for the role of these polymorphisms in panic disorder.