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

TLDR

Genetic studies implicate monoamine oxidase A on the X chromosome as a candidate for panic disorder, given the efficacy of MAO‑A inhibitors. The study examined whether a novel promoter repeat polymorphism of the MAO‑A gene associates with panic disorder in German and Italian cohorts. Researchers genotyped the promoter repeat in patients and controls and used luciferase assays to compare allele transcriptional activity. The 3a, 4, and 5 repeat alleles were more transcriptionally active and occurred more often in female panic disorder patients, indicating that higher MAO‑A activity is a risk factor.

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, 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.