Hattori E, Yamada K, Toyota T, Yoshitsugu K, Toru M, Shibuya H, Yoshikawa T
Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Wako, Saitama, Japan.
Am J Med Genet. 2001 Dec 8;105(8):779-82. doi: 10.1002/ajmg.10043.
The tetrapeptide of cholecystokinin (CCK), CCK-4, is known to induce panic attacks in human subjects, while CCK-8 is reported to have a therapeutic effect on schizophrenia symptoms. Recently, we have identified a novel microsatellite polymorphism in the 5' upstream region of the CCK gene and shown a significant association between this polymorphism and panic disorder. In this study, we have investigated the CCK-B receptor (CCKBR) gene, which is the main constituent of the CCK receptor in the CNS. Recently, a dinucleotide repeat, (CT)(n), in the 5' regulatory region of the CCKBR gene was reported to be associated with panic disorder in Canadian samples. To evaluate an association of the CT repeat with panic disorder and schizophrenia, we genotyped 71 subjects with panic disorder, 154 schizophrenics and 199 controls. However, no evidence of allelic association was found between the polymorphic repeat of the CCKBR gene and either panic disorder or schizophrenia (P = 0.186 and 0.987, respectively). Together with the negative reports on association analyses using other polymorphisms of the CCKBR gene and Japanese samples, the present results exclude a major genetic contribution of the CCKBR gene to susceptibilities to panic disorder and schizophrenia in Japanese cohorts.
已知胆囊收缩素（CCK）的四肽CCK - 4可在人类受试者中诱发惊恐发作，而CCK - 8据报道对精神分裂症症状具有治疗作用。最近，我们在CCK基因5'上游区域鉴定出一种新的微卫星多态性，并表明这种多态性与惊恐障碍之间存在显著关联。在本研究中，我们研究了CCK - B受体（CCKBR）基因，它是中枢神经系统中CCK受体的主要成分。最近，据报道CCKBR基因5'调控区域中的二核苷酸重复序列（CT）（n）与加拿大样本中的惊恐障碍有关。为了评估CT重复序列与惊恐障碍和精神分裂症的关联，我们对71名惊恐障碍患者、154名精神分裂症患者和199名对照进行了基因分型。然而，在CCKBR基因的多态性重复序列与惊恐障碍或精神分裂症之间均未发现等位基因关联的证据（P值分别为0.186和0.987）。连同使用CCKBR基因的其他多态性和日本样本进行关联分析的阴性报告，目前的结果排除了CCKBR基因对日本人群中惊恐障碍和精神分裂症易感性的主要遗传贡献。
