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Association of cholecystokinin‐A receptor gene polymorphisms and panic disorder in Japanese
Author(s) -
Miyasaka Kyoko,
Yoshida Yuki,
Matsushita Sachio,
Higuchi Susumu,
Shirakawa Osamu,
Shimokata Hiroshi,
Funakoshi Akihiro
Publication year - 2004
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.20160
Subject(s) - haplotype , genotype , cholecystokinin , single nucleotide polymorphism , genetics , biology , gene , polymorphism (computer science) , panic disorder , genbank , receptor , medicine , psychiatry , anxiety
Several lines of evidence have suggested that naturally occurring alterations in cholecystokinin (CCK) systems could contribute to the development of panic disorder (PD). Among recent investigations, polymorphisms of the CCK and CCK‐B receptor (R) genes were investigated, but the results were inconclusive. We recently cloned the genomic structures of human CCK‐AR, and determined the transcriptional start site of the human CCK‐AR gene. Two sequence changes were detected in the promoter region: a G to T change in nucleotide −128 and an A to G change in nucleotide −81 (GenBank database under accession number D85606). The frequencies of the genotypes and haplotypes of these two polymorphisms were compared in 109 Japanese patients with PD and 400 age‐ and gender‐matched normal Japanese control subjects. The frequency of variant genotypes (−81A/G, −128G/T; G/G, G/T, and G/G, T/T) having variant haplotype (−81G/−128T) was significantly higher in PD than in controls ( P < 0.0001, OR = 2.81, 95% CI = 1.74–4.39). The statistical differences between the haplotype distributions in the PD and control groups were highly significant: the frequency of variant haplotype (−81G/−128T) was higher in the former group than in the latter ( P < 0.0001). This association was not affected by clinical characteristics such as age, gender, and age at onset of PD. In this study, the first to report the positive association of the CCK‐AR polymorphisms and PD, haplotype analyses further strengthened the association based on our comparison of genotype distributions. The CCK‐AR gene polymorphism may be involved in the neurobiology of PD. © 2004 Wiley‐Liss, Inc.