Human Molecular Genetics, Vol 8, 621-624, Copyright © 1999 by Oxford University Press
J Deckert, M Catalano, YV Syagailo, M Bosi, O Okladnova, D Di Bella, MM Nothen, P Maffei, P Franke, J Fritze, W Maier, P Propping, H Beckmann, L Bellodi and KP Lesch
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.
ARTICLES
Excess of high activity monoamine oxidase A gene promoter alleles in female patients with panic disorder
Department of Psychiatry, University of Wurzburg, Fuchsleinstrasse 15, 97080 Wurzburg, Germany, Istituto di Ricovero e Cura a Carattere Scientifico H San Raffaele, DSNP, Via Prinetti 29, 20127 Milan, Italy. deckert@rzbox.uni-wuerzberg.de
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