Effect of MAOA DNA Methylation on Human in Vivo Protein Expression Measured by [11C]harmine Positron Emission Tomography.
MAOA
DNA methylation
monoamine oxidase A
positron emission tomography
seasonal affective disorder
Journal
The international journal of neuropsychopharmacology
ISSN: 1469-5111
Titre abrégé: Int J Neuropsychopharmacol
Pays: England
ID NLM: 9815893
Informations de publication
Date de publication:
14 02 2023
14 02 2023
Historique:
received:
12
08
2022
accepted:
26
12
2022
pubmed:
28
12
2022
medline:
16
2
2023
entrez:
27
12
2022
Statut:
ppublish
Résumé
Epigenetic modifications like DNA methylation are understood as an intermediary between environmental factors and neurobiology. Cerebral monoamine oxidase A (MAO-A) levels are altered in depression, as are DNA methylation levels within the MAOA gene, particularly in the promoter/exon I/intron I region. An effect of MAOA methylation on peripheral protein expression was shown, but the extent to which methylation affects brain MAO-A levels is not fully understood. Here, the influence of MAOA promoter/exon I/intron I region DNA methylation on global MAO-A distribution volume (VT), an index of MAO-A density, was assessed via [11C]harmine positron emission tomography in 22 patients (14 females) suffering from seasonal affective disorder and 30 healthy controls (17 females). No significant influence of MAOA DNA methylation on global MAO-A VT was found, despite correction for health status, sex, season, and MAOA variable number of tandem repeat genotype. However, season affected average methylation in women, with higher levels in spring and summer (Puncorr = .03). We thus did not find evidence for an effect of MAOA DNA methylation on brain MAO-A VT. In contrast to a previous study demonstrating an effect of methylation of a MAOA promoter region located further 5' on brain MAO-A, MAOA methylation of the region assessed here appears to affect brain protein levels to a limited extent at most. The observed effect of season on methylation levels is in accordance with extensive evidence for seasonal effects within the serotonergic system. NCT02582398 (https://clinicaltrials.gov/ct2/show/NCT02582398).
Sections du résumé
BACKGROUND
Epigenetic modifications like DNA methylation are understood as an intermediary between environmental factors and neurobiology. Cerebral monoamine oxidase A (MAO-A) levels are altered in depression, as are DNA methylation levels within the MAOA gene, particularly in the promoter/exon I/intron I region. An effect of MAOA methylation on peripheral protein expression was shown, but the extent to which methylation affects brain MAO-A levels is not fully understood.
METHODS
Here, the influence of MAOA promoter/exon I/intron I region DNA methylation on global MAO-A distribution volume (VT), an index of MAO-A density, was assessed via [11C]harmine positron emission tomography in 22 patients (14 females) suffering from seasonal affective disorder and 30 healthy controls (17 females).
RESULTS
No significant influence of MAOA DNA methylation on global MAO-A VT was found, despite correction for health status, sex, season, and MAOA variable number of tandem repeat genotype. However, season affected average methylation in women, with higher levels in spring and summer (Puncorr = .03). We thus did not find evidence for an effect of MAOA DNA methylation on brain MAO-A VT.
CONCLUSIONS
In contrast to a previous study demonstrating an effect of methylation of a MAOA promoter region located further 5' on brain MAO-A, MAOA methylation of the region assessed here appears to affect brain protein levels to a limited extent at most. The observed effect of season on methylation levels is in accordance with extensive evidence for seasonal effects within the serotonergic system.
CLINICALTRIALS.GOV IDENTIFIER
NCT02582398 (https://clinicaltrials.gov/ct2/show/NCT02582398).
Identifiants
pubmed: 36573644
pii: 6961527
doi: 10.1093/ijnp/pyac085
pmc: PMC9926052
doi:
Substances chimiques
Harmine
4FHH5G48T7
Monoamine Oxidase
EC 1.4.3.4
Carbon-11
0
Carbon Radioisotopes
0
Banques de données
ClinicalTrials.gov
['NCT02582398']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
116-124Subventions
Organisme : Austrian Science Fund FWF
ID : DOC 33
Pays : Austria
Organisme : Austrian Science Fund FWF
ID : KLI 504
Pays : Austria
Informations de copyright
© The Author(s) 2022. Published by Oxford University Press on behalf of CINP.
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