Abstract
The cholecystokinin gene (CCK) is thought to play a role in the pathogenesis of both panic disorder1–4 and schizophrenia.5 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.
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Acknowledgements
We thank Dr Joanne Meerabux for her critical reading of the manuscript. This study was partly supported by the Grant-in-Aid for Encouragement of Young Scientists, Ministry of Education, Japan (No. 12770554) to Kazuo Yamada.
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Hattori, E., Ebihara, M., Yamada, K. et al. 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. Mol Psychiatry 6, 465–470 (2001). https://doi.org/10.1038/sj.mp.4000875
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DOI: https://doi.org/10.1038/sj.mp.4000875
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