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.
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.
Hattori
E
E
Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan.
Ebihara
M
M
Yamada
K
K
Ohba
H
H
Shibuya
H
H
Yoshikawa
T
T
D020121:5' Untranslated Regions / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001483:Base Sequence; D002766:Cholecystokinin / Q000235:genetics*; D004247:DNA / Q000737:chemistry / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009010:Monte Carlo Method; D016584:Panic Disorder / Q000235:genetics*; D011110:Polymorphism, Genetic; D012016:Reference Values; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*
D020121:5' Untranslated Regions; D004247:DNA; D002766:Cholecystokinin