Identification of a compound short tandem repeat stretch in the 5′-upstream region of the cholecystokinin gene, and its association with panic disorder but not with schizophrenia
- 1 July 2001
- journal article
- research article
- Published by Springer Nature in Molecular Psychiatry
- Vol. 6 (4), 465-470
- https://doi.org/10.1038/sj.mp.4000875
Abstract
The cholecystokinin gene (CCK) is thought to play a role in the pathogenesis of both panic disorder and schizophrenia. In this study, we have extended the 5'-upstream sequence of the CCK gene, and identified a compound short tandem repeat (STR), located approximately -2.2 to -1.8 kb from the cap site. This STR was found to be polymorphic with ten different allele lengths. Case-control studies using 73 panic patients, 305 schizophrenics and 252 controls showed a significant allelic association with panic disorder (P = 0.025), but not with schizophrenia. Dividing the STR alleles into three classes according to length, Long (L), Medium (M) and Short (S), produced strong genotypic (MM) (nominal P = 0.0014) and allelic (M) (nominal P = 0.0079) associations with panic disorder. screening the newly extended promoter region detected not only the previously identified -36c>t and -188a>g single nucleotide polymorphisms (SNPs) but a new rare snp, -345g>C. Neither of the former two SNPs showed significant association with either panic disorder or schizophrenia. Haplotypic distributions of the STR and SNPs -188 and -36 were significantly different between panic samples and controls (P = 0.0003). These findings suggest that the novel STR or a nearby variant may confer susceptibility to the development of panic disorder.Keywords
This publication has 23 references indexed in Scilit:
- Function of the C−36 to T polymorphism in the human cholecystokinin gene promoterMolecular Psychiatry, 2000
- Use of Unlinked Genetic Markers to Detect Population Stratification in Association StudiesAmerican Journal of Human Genetics, 1999
- Linked polymorphisms upstream of exons 1 and 2 of the human cholecystokinin gene are not associated with schizophrenia or bipolar disorderMolecular Psychiatry, 1998
- Association of Anxiety-Related Traits with a Polymorphism in the Serotonin Transporter Gene Regulatory RegionScience, 1996
- Transcriptional Regulation of the Human Cholecystokinin Gene: Composite Action of Upstream Stimulatory Factor, Sp1, and Members of the CREB/ATF-AP-1 Family of Transcription FactorsDNA and Cell Biology, 1996
- Monte Carlo tests for associations between disease and alleles at highly polymorphic lociAnnals of Human Genetics, 1995
- A twin study of DSM‐III‐R anxiety disordersActa Psychiatrica Scandinavica, 1993
- Molecular Cloning, Functional Expression and Chromosomal Localization of the Human Cholecystokinin Type A ReceptorBiochemical and Biophysical Research Communications, 1993
- Structure of human cholecystokinin gene and its chromosomal locationGene, 1986
- Evidence for coexistence of dopamine and CCK in meso-limbic neuronesNature, 1980