Meta‐analysis argues for a female‐specific role of MAOA‐uVNTR in panic disorder in four European populations

Medientyp: E-Artikel
Titel: Meta‐analysis argues for a female‐specific role of MAOA‐uVNTR in panic disorder in four European populations
Beteiligte: Reif, Andreas; Weber, Heike; Domschke, Katharina; Klauke, Benedikt; Baumann, Christian; Jacob, Christian P.; Ströhle, Andreas; Gerlach, Alexander L.; Alpers, Georg W.; Pauli, Paul; Hamm, Alfons; Kircher, Tilo; Arolt, Volker; Wittchen, Hans‐Ulrich; Binder, Elisabeth B.; Erhardt, Angelika; Deckert, Jürgen
Erschienen: Wiley, 2012
Erschienen in: American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
Sprache: Englisch
DOI: 10.1002/ajmg.b.32085
ISSN: 1552-4841; 1552-485X
Schlagwörter: Cellular and Molecular Neuroscience ; Psychiatry and Mental health ; Genetics (clinical)
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Beschreibung: <jats:title>Abstract</jats:title><jats:p>Panic disorder (PD) is a common mental disorder, ranking highest among the anxiety disorders in terms of disease burden. The pathogenesis of PD is multifactorial with significant heritability, however only a few convincing risk genes have been reported thus far. One of the most promising candidates is the gene encoding monoamine oxidase A (<jats:italic>MAOA</jats:italic>), due to its key role in monoaminergic neurotransmission, established validity of animal models, and the efficacy of MAO inhibitors in the treatment of PD. A promoter repeat polymorphism in <jats:italic>MAOA</jats:italic> (<jats:italic>MAOA</jats:italic>‐uVNTR) impacts on gene expression; high‐expression alleles have been reported to increase the risk for PD. To further scrutinize the role of this polymorphism, we performed a formal meta‐analysis on <jats:italic>MAOA</jats:italic>‐uVNTR and PD using original data from four published European (Estonian, German, Italian, and Polish) samples and genotypes from three hitherto unpublished German PD samples, resulting in the largest (n = 1,115 patients and n = 1,260 controls) genetic study on PD reported to date. In the unpublished samples, evidence for association of <jats:italic>MAOA</jats:italic>‐uVNTR with PD was obtained in one of the three samples. Results of the meta‐analysis revealed a significant and female‐specific association when calculating an allelic model (OR = 1.23, <jats:italic>P</jats:italic> = 0.006). This sex‐specific effect might be explained by a gene‐dose effect causing higher <jats:italic>MAOA</jats:italic> expression in females. Taken together, our meta‐analysis therefore argues that high‐expression <jats:italic>MAOA</jats:italic>‐uVNTR alleles significantly increase the risk towards PD in women. However, epigenetic mechanisms might obfuscate the genetic association, calling for ascertainment in larger samples as well as assessment of the <jats:italic>MAOA</jats:italic> promoter methylation status therein. © 2012 Wiley Periodicals, Inc.</jats:p>

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