Possible association of a cholecystokinin promotor polymorphism (CCK-36CT) with panic disorder

• Main Authors: Wang, Z, Valdes, J, Noyes, R, Zoega, T, Crowe, R R
• Other Authors: Department of Psychiatry, University of Iowa College of Medicine, Iowa City 52242-1000, USA.
• Format: Article in Journal/Newspaper
• Language: English
• Published: Wiley-Liss 2010
• Subjects: Adult; Cholecystokinin; DNA Mutational Analysis; Exons; Female; Gene Frequency; Humans; Iceland; Iowa; Linkage (Genetics); Male; Middle Aged; Panic Disorder; Pedigree; Point Mutation; Polymorphism; Single-Stranded Conformational; Promoter Regions; Genetic
• Online Access: http://hdl.handle.net/2336/108541; https://doi.org/10.1002/(SICI)1096-8628(19980508)81:3<228::AID-AJMG5>3.0.CO;2-S

To access publisher full text version of this article. Please click on the hyperlink in Additional Links field We searched for mutations in the CCK gene in panic disorder with single-strand conformational polymorphism (SSCP) analysis of the three exons and promotor region of the gene. We found a C-->T transition at position -36 (CCK(-36C-->T)) in a GC box, a binding site for transcription factor Sp1, in the promotor region. The allele frequency was 0.168 (95% CI, 0.116-0.221) in 98 persons with panic disorder and 0.083 (95% CI, 0.059-0.107) in 247 geographically matched, unscreened controls. A transmission disequilibrium test based on panic disorder as the affected phenotype was nonsignificant (chi2 = 0.93), but when panic disorder or attacks were considered as affected, statistically significant transmission disequilibrium was detected (chi2 = 4.00, P < 0.05). Linkage analysis was uninformative. In exploratory analyses to search for clinical correlations, the "T" allele was found in 59% of 22 persons with panic attacks but not panic disorder, compared with 31% of those who met the criteria for panic disorder. An association between the CCK polymorphism and panic disorder cannot be considered established due to the inconsistencies in the results noted above, but if the provisional association can be replicated, the findings are consistent with CCK(-36C-->T) being a disease-susceptibility allele that alone is neither necessary nor sufficient to cause panic disorder but that increases vulnerability by acting epistatically.