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Hum Mol Genet. 1999 Apr;8(4):621-4.

Excess of high activity monoamine oxidase A gene promoter alleles in female patients with panic disorder.

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  • 1Department 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. deckert@rzbox.uni-wuerzberg.de

Abstract

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.

PMID:
10072430
[PubMed - indexed for MEDLINE]
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