Hamilton S P, Slager S L, Helleby L, Heiman G A, Klein D F, Hodge S E, Weissman M M, Fyer A J, Knowles J A
Department of Psychiatry, College of Physicians and Surgeons at Columbia University and the New York State Psychiatric Institute, USA.
Mol Psychiatry. 2001 Jan;6(1):59-65. doi: 10.1038/sj.mp.4000788.
Growing animal data implicate cholecystokinin in the regulation of anxiety, while human clinical research confirms the role of cholecystokinin in the provocation of panic attacks. Antipanic medications suppress the ability of cholecystokinin to induce panic attacks, and may alter the expression of the cholecystokinin gene. Thus, there is increased interest in understanding the molecular genetic component of these observations. Recent association studies using persons with panic disorder described some association between polymorphisms in the genes encoding cholecystokinin and the cholecystokinin B-receptor and panic disorder. In this study, we used a family-based design, employing 596 individuals in 70 panic disorder pedigrees, as well as 77 haplotype relative risk 'triads'. Subjects were genotyped for two polymorphisms: the polymorphic microsatellite marker in the CCK-BR locus using PCR-based genotyping and at a single nucleotide polymorphism in the CCK promoter using a fluorescence polarization detection assay, and the data were analyzed for genetic association and linkage. Employing a variety of diagnostic and genetic models, linkage analysis produced no significant lod scores at either locus. Family-based tests of association, the haplotype-based haplotype relative risk statistic and the transmission disequilibrium test, were likewise non-significant. The results reported here provide little support for the role of these polymorphisms in panic disorder.
不断增加的动物实验数据表明胆囊收缩素参与焦虑调节，而人体临床研究证实胆囊收缩素在引发惊恐发作中起作用。抗惊恐药物可抑制胆囊收缩素诱发惊恐发作的能力，并可能改变胆囊收缩素基因的表达。因此，人们对了解这些观察结果的分子遗传学成分越来越感兴趣。最近针对惊恐障碍患者开展的关联研究描述了编码胆囊收缩素的基因和胆囊收缩素B受体中的多态性与惊恐障碍之间存在某种关联。在本研究中，我们采用基于家系的设计，纳入了70个惊恐障碍家系中的596名个体以及77个单倍型相对风险“三联体”。对受试者进行了两种多态性的基因分型：使用基于聚合酶链反应的基因分型对CCK - BR基因座中的多态性微卫星标记进行分型，并使用荧光偏振检测法对CCK启动子中的单核苷酸多态性进行分型，然后对数据进行遗传关联和连锁分析。采用各种诊断和遗传模型，连锁分析在两个基因座均未产生显著的对数优势分数。基于家系的关联检验、基于单倍型的单倍型相对风险统计以及传递不平衡检验同样无显著结果。此处报告的结果几乎不支持这些多态性在惊恐障碍中的作用。
