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Methylation of the SLC6a2 gene promoter in major depression and panic disorder

Bayles, Richard ; Baker, Emma K ; Jowett, Jeremy B M ; Barton, David ; Esler, Murray ; El-Osta, Assam ; Lambert, Gavin Tost, Jorg

PloS one, 2013-12, Vol.8 (12), p.e83223-e83223 [Periódico revisado por pares]

United States: Public Library of Science

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Methylation of the SLC6a2 gene promoter in major depression and panic disorder
Autor: Bayles, Richard ; Baker, Emma K ; Jowett, Jeremy B M ; Barton, David ; Esler, Murray ; El-Osta, Assam ; Lambert, Gavin
Tost, Jorg
Assuntos: Adult ; Aging ; Analysis ; Anxiety ; Binding sites ; CpG islands ; Deoxyribonucleic acid ; Depressive Disorder, Major - genetics ; Diabetes ; Disease ; DNA ; DNA methylation ; DNA Methylation - genetics ; DNA sequencing ; Epigenetics ; Female ; Gene expression ; Gene regulation ; Gene sequencing ; Gene silencing ; Genetic aspects ; Genetic diversity ; Genetic testing ; Genomes ; Heart ; Humans ; Hypotheses ; Laboratories ; Major depressive disorder ; Male ; Mental depression ; Methylation ; Middle Aged ; Nervous system ; Noradrenaline ; Norepinephrine ; Norepinephrine Plasma Membrane Transport Proteins - genetics ; Nucleotide sequence ; Panic ; Panic attacks ; Panic disorder ; Panic Disorder - genetics ; Panic disorders ; Patients ; Physiological aspects ; Promoter Regions, Genetic - genetics ; Promoters (Genetics) ; Studies ; Substance abuse treatment
É parte de: PloS one, 2013-12, Vol.8 (12), p.e83223-e83223
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
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Competing Interests: The authors have read the journal's policy and have the following conflicts: The laboratories of Professors Lambert and Esler currently receive research funding from Medtronic, Abbott Pharmaceuticals, Servier Australia and Allergan. Professor Lambert has acted as a consultant for Medtronic and has received honoraria or travel support for presentations from Pfizer, Wyeth Pharmaceuticals, Servier and Medtronic. Professor Esler serves on scientific advisory boards of Abbott (formerly Solvay) Pharmaceuticals and Medtronic. Associate Professor Barton has received honoraria or travel support from Pfizer, Servier, Astra Zeneca, Lilly, Novartis, Janssen Cilag and Lundbeck. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.
Conceived and designed the experiments: RB EKB JBMJ DB ME AE-O GL. Performed the experiments: RB EKB. Analyzed the data: RB EKB AE-O GL. Contributed reagents/materials/analysis tools: RB EKB JBMJ ME AE-O GL. Wrote the manuscript: RB EKB DB ME AE-O GL.
Descrição: Reduced function of the noradrenaline transporter (NET) has been demonstrated in patients with major depressive disorder (MDD) and panic disorder. Attempts to explain NET dysfunction in MDD and panic disorder by genetic variation in the NET gene SLC6a2 have been inconclusive. Transcriptional silencing of the SLC6a2 gene may be an alternative mechanism which can lead to NET dysfunction independent of DNA sequence. The objective of this study was to characterise the DNA methylation state of the SLC6a2 gene promoter in patients with MDD and panic disorder. SLC6a2 promoter methylation was also analysed before and after antidepressant treatment. This study was performed with DNA from blood, using bisulphite sequencing and EpiTYPER methylation analyses. Patients with MDD or panic disorder were not found to differ significantly from healthy controls in the pattern of methylation of the SLC6a2 gene promotor. While significant correlations between methylation levels at some CpG sites and physiological measures were identified, overall the variation in DNA methylation between patients was small, and the significance of this variation remains equivocal. No significant changes in SLC6a2 promoter methylation were observed in response to antidepressant treatment. Further in-depth analysis of alternative mechanisms of transcriptional regulation of the SLC6a2 gene in human health and disease would be of value.
Editor: United States: Public Library of Science
Idioma: Inglês

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Methylation of the SLC6a2 gene promoter in major depression and panic disorder

Bayles, Richard ; Baker, Emma K ; Jowett, Jeremy B M ; Barton, David ; Esler, Murray ; El-Osta, Assam ; Lambert, Gavin Tost, Jorg

United States: Public Library of Science

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