Gene variations in the cholecystokinin system in patients with panic disorder
- 1 April 2010
- journal article
- research article
- Published by Wolters Kluwer Health in Psychiatric Genetics
- Vol. 20 (2), 59-64
- https://doi.org/10.1097/ypg.0b013e32833511a8
Abstract
Objectives Panic disorder (PD) is a common psychiatric disease occurring more frequently in women than men. Multiple common and/or rare variants in the genome contribute to the complex etiology of the disorder. The neuropeptide cholecystokinin (CCK) and its receptors (the CCK system) have been suggested to be involved in the pathogenesis of PD. Methods We examined the promoter, exon, and exon–intron boundaries of the genes encoding CCK and its receptors (CCKAR and CCKBR) for variations in 187 patients with PD and 277 screened control individuals. Up to 1342 additional healthy population controls were examined for some of the variations. One CCK gene intron variation was analyzed for alternative splicing using an exon-trapping assay. Results The promoter variant (−36C > T; rs1799923) and an intron 1 polymorphism (IVS1-7C > G; rs754635) in the CCK gene were found to protect against PD (PP=0.004). In addition, we found two novel rare missense variations in the CCKBR gene (Lys329Asn and Pro446Leu) in two and one patient, respectively. Conclusion The results suggest that the CCK system may play a role in the pathogenesis of PD, with susceptibility alleles both protecting and contributing to the disease. Both common and rare variants seem to be involved. The involvement of the CCK system may also contribute to the increased prevalence of PD in women.Keywords
This publication has 41 references indexed in Scilit:
- Identification of new putative susceptibility genes for several psychiatric disorders by association analysis of regulatory and non‐synonymous SNPs of 306 genes involved in neurotransmission and neurodevelopmentAmerican Journal Of Medical Genetics Part B-Neuropsychiatric Genetics, 2009
- Evaluation of the CCK-4 model as a challenge paradigm in a population of healthy volunteers within a proof-of-concept studyPsychopharmacology, 2007
- HUMAN MIGRATIONS AND POPULATION STRUCTURE: What We Know and Why it MattersAnnual Review of Genomics and Human Genetics, 2002
- The Structure of Haplotype Blocks in the Human GenomeScience, 2002
- Idiopathic environmental intolerance: Increased prevalence of panic disorder–associated cholecystokinin B receptor allele 7Journal of Allergy and Clinical Immunology, 2001
- No association or linkage between polymorphisms in the genes encoding cholecystokinin and the cholecystokinin B receptor and panic disorderMolecular Psychiatry, 2000
- Population genetics—making sense out of sequenceNature Genetics, 1999
- Isolation of genes from complex sources of mammalian genomic DNA using exon amplificationNature Genetics, 1994
- Enhanced Sensitivity to Cholecystokinin Tetrapeptide in Panic DisorderArchives of General Psychiatry, 1991
- Cholecystokinin Tetrapeptide Induces Panic-like Attacks in Healthy VolunteersArchives of General Psychiatry, 1989