Hattori E, Ebihara M, Yamada K, Ohba H, Shibuya H, Yoshikawa T
Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan.
Mol Psychiatry. 2001 Jul;6(4):465-70. doi: 10.1038/sj.mp.4000875.
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.
胆囊收缩素基因（CCK）被认为在惊恐障碍和精神分裂症的发病机制中起作用。在本研究中，我们扩展了CCK基因的5'上游序列，并鉴定出一个复合短串联重复序列（STR），其位于距帽位点约-2.2至-1.8 kb处。发现该STR具有多态性，有十种不同的等位基因长度。对73名惊恐障碍患者、305名精神分裂症患者和252名对照进行的病例对照研究表明，该STR与惊恐障碍存在显著的等位基因关联（P = 0.025），但与精神分裂症无关。根据长度将STR等位基因分为三类，长（L）、中（M）和短（S），结果显示与惊恐障碍存在强烈的基因型（MM）（名义P = 0.0014）和等位基因（M）（名义P = 0.0079）关联。对新扩展的启动子区域进行筛查，不仅检测到先前鉴定的-36c>t和-188a>g单核苷酸多态性（SNP），还发现了一个新的罕见SNP，-345g>C。前两个SNP均未显示与惊恐障碍或精神分裂症有显著关联。惊恐样本与对照之间，STR以及SNP -188和-36的单倍型分布存在显著差异（P = 0.0003）。这些发现表明，新的STR或其附近的变异可能使个体易患惊恐障碍。
