title: Effects of promoter methylation on increased expression of polyamine biosynthetic genes in suicide.
abstract: Suicide is among the leading causes of death worldwide. The polyamine system has been increasingly implicated in the neurobiology of suicide. Previous research has indicated that epigenetic mechanisms play a role in explaining dysregulation of polyamine genes in suicide completers. Nevertheless, regulatory mechanisms explaining polyamine biosynthetic genes displaying dysregulated expression in suicide completers, including ornithine decarboxylase antizymes 1 and 2 (OAZ1 and OAZ2), S-adenosylmethionine decarboxylase (AMD1), and arginase 2 (ARG2), have yet to be elucidated. In this study, we investigated methylation patterns in the promoter region of OAZ1, OAZ2, AMD1, and ARG2 in Brodmann area 44 from a group of 33 suicide completers and 31 non-suicide controls. We found significant site-specific differences in methylation in the promoter of ARG2 and AMD1 that were also significantly negatively correlated with gene expression. These findings provide further support for a role for the involvement of epigenetic modifications in the regulation of genes associated with polyamine biosynthesis, and which may contribute to the complexity of suicidal behaviors.
authors.affiliation: McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, 6875 boul. Lasalle, Verdun, Quebec H4H 1R3, Canada.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Gross
authors.forename: Laura M
authors.initials: LM
authors.lastname: Fiori
authors.forename: Benoit
authors.initials: B
authors.lastname: Labonté
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Lopez
authors.forename: Gustavo
authors.initials: G
authors.lastname: Turecki
mesh_terms: D012437:Adenosylmethionine Decarboxylase / Q000235:genetics*; D000328:Adult; D001119:Arginase / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000235:genetics; D057890:Epigenomics; D015870:Gene Expression / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D008297:Male; D011073:Polyamines; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D013405:Suicide
chemical_list: D011073:Polyamines; D011506:Proteins; C031017:ornithine decarboxylase antizyme; D001119:Arginase; D012437:Adenosylmethionine Decarboxylase