DNA hypomethylation of Synapsin II CpG islands associates with increased gene expression in bipolar disorder and major depression.

TitleDNA hypomethylation of Synapsin II CpG islands associates with increased gene expression in bipolar disorder and major depression.
Publication TypeJournal Article
Year of Publication2016
AuthorsCruceanu C, Kutsarova E, Chen ES, Checknita DR, Nagy C, Lopez JPablo, Alda M, Rouleau GA, Turecki G
JournalBMC Psychiatry
Volume16
Issue1
Pagination286
Date Published2016 Aug 11
ISSN1471-244X
Abstract

BACKGROUND: The Synapsins (SYN1, SYN2, and SYN3) are important players in the adult brain, given their involvement in synaptic transmission and plasticity, as well as in the developing brain through roles in axon outgrowth and synaptogenesis. We and others previously reported gene expression dysregulation, both as increases and decreases, of Synapsins in mood disorders, but little is known about the regulatory mechanisms leading to these differences. Thus, we proposed to study DNA methylation at theses genes' promoter regions, under the assumption that altered epigenetic marks at key regulatory sites would be the cause of gene expression changes and thus part of the mood disorder etiology.METHODS: We performed CpG methylation mapping focusing on the three genes' predicted CpG islands using the Sequenom EpiTYPER platform. DNA extracted from post-mortem brain tissue (BA10) from individuals who had lived with bipolar disorder (BD), major depressive disorder (MDD), as well as psychiatrically healthy individuals was used. Differences in methylation across all CpGs within a CpG island and between the three diagnostic groups were assessed by 2-way mixed model analyses of variance.RESULTS: We found no significant results for SYN1 or SYN3, but there was a significant group difference in SYN2 methylation, as well as an overall pattern of hypomethylation across the CpG island. Furthermore, we found a significant inverse correlation of DNA methylation with SYN2a mRNA expression.CONCLUSIONS: These findings contribute to previous work showing dysregulation of Synapsins, particularly SYN2, in mood disorders and improve our understanding of the regulatory mechanisms that precipitate these changes likely leading to the BD or MDD phenotype.

DOI10.1186/s12888-016-0989-0
Alternate JournalBMC Psychiatry
PubMed ID27515700
PubMed Central IDPMC4982122
Grant ListR01 DA033684 / DA / NIDA NIH HHS / United States

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