Deckert J, Catalano M, Syagailo Y V, Bosi M, Okladnova O, Di Bella D, Nöthen M M, Maffei P, Franke P, Fritze J, Maier W, Propping P, Beckmann H, Bellodi L, Lesch K P
Department of Psychiatry, University of Würzburg, Füchsleinstrasse 15, 97080 Würzburg, Germany, Istituto di Ricovero e Cura a Carattere Scientifico H San Raffaele, DSNP, Via Prinetti 29, 20127 Milan, Italy.
Hum Mol Genet. 1999 Apr;8(4):621-4. doi: 10.1093/hmg/8.4.621.
A genetic contribution to the pathogenesis of panic disorder has been demonstrated by clinical genetic studies. Molecular genetic studies have focused on candidate genes suggested by the molecular mechanisms implied in the action of drugs utilized for therapy or in challenge tests. One class of drugs effective in the treatment of panic disorder is represented by monoamine oxidase A inhibitors. Therefore, the monoamine oxidase A gene on chromosome X is a prime candidate gene. In the present study we investigated a novel repeat polymorphism in the promoter of the monoamine oxidase A gene for association with panic disorder in two independent samples (German sample, n = 80; Italian sample, n = 129). Two alleles (3 and 4 repeats) were most common and constituted >97% of the observed alleles. Functional characterization in a luciferase assay demonstrated that the longer alleles (3a, 4 and 5) were more active than allele 3. Among females of both the German and the Italian samples of panic disorder patients (combined, n = 209) the longer alleles (3a, 4 and 5) were significantly more frequent than among females of the corresponding control samples (combined, n = 190, chi2 = 10.27, df = 1, P = 0.001). Together with the observation that inhibition of monoamine oxidase A is clinically effective in the treatment of panic disorder these findings suggest that increased monoamine oxidase A activity is a risk factor for panic disorder in female patients.
临床遗传学研究已证实惊恐障碍的发病机制存在遗传因素。分子遗传学研究聚焦于治疗用药或激发试验作用所涉及分子机制提示的候选基因。一类有效治疗惊恐障碍的药物以单胺氧化酶A抑制剂为代表。因此，X染色体上的单胺氧化酶A基因是主要候选基因。在本研究中，我们在两个独立样本（德国样本，n = 80；意大利样本，n = 129）中研究了单胺氧化酶A基因启动子中的一种新型重复多态性与惊恐障碍的关联性。两个等位基因（3次和4次重复）最为常见，占观察到的等位基因的97%以上。荧光素酶测定中的功能特性表明，较长的等位基因（3a、4和5）比等位基因3更具活性。在德国和意大利惊恐障碍患者样本的女性中（合并样本，n = 209），较长的等位基因（3a、4和5）明显比相应对照样本的女性更常见（合并样本，n = 190，χ2 = 10.27，自由度 = 1，P = 0.001）。连同单胺氧化酶A抑制在惊恐障碍治疗中具有临床疗效这一观察结果，这些发现提示单胺氧化酶A活性增加是女性患者患惊恐障碍的一个风险因素。
