Excess of High Activity Monoamine Oxidase A Gene Promoter Alleles in Female Patients with Panic Disorder

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 drug...

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Published in:Human molecular genetics 1999-04, Vol.8 (4), p.621-624
Main Authors: Deckert, Jürgen, Catalano, Marco, Syagailo, Yana V., Bosi, Monica, Okladnova, Olga, Di Bella, Daniela, Nöthen, Markus M., Maffei, Piermario, Franke, Petra, Fritze, Jürgen, Maier, Wolfgang, Propping, Peter, Beckmann, Helmut, Bellodi, Laura, Lesch, Klaus-Peter
Format: Article
Language:English
Subjects:
Adult and adolescent clinical studies
Alleles
Anxiety disorders. Neuroses
Biological and medical sciences
Classical genetics, quantitative genetics, hybrids
Data Interpretation, Statistical
DNA, Recombinant - genetics
DNA, Recombinant - metabolism
Female
Fundamental and applied biological sciences. Psychology
Gene Expression Regulation, Enzymologic
Gene Frequency
Genetics of eukaryotes. Biological and molecular evolution
Genotype
Human
Humans
Luciferases - genetics
Male
Medical sciences
monoamine oxidase
Monoamine Oxidase - genetics
Panic disorder
Panic Disorder - genetics
Polymorphism, Genetic
Promoter Regions, Genetic - genetics
Psychology. Psychoanalysis. Psychiatry
Psychopathology. Psychiatry
Sex Factors
Tumor Cells, Cultured
X chromosome
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Summary: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, χ2 = 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.
ISSN:0964-6906
1460-2083
DOI:10.1093/hmg/8.4.621