McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada.
Int J Neuropsychopharmacol. 2010 Jul;13(6):725-36. doi: 10.1017/S1461145709991167. Epub 2010 Jan 11.
Alterations in the levels of spermine synthase (SMS) and spermine oxidase (SMOX), two enzymes involved in polyamine metabolism, have previously been observed in brains of suicide completers. To characterize the roles played by genetic and epigenetic factors in determining expression levels of these genes, as well as to identify potential mechanisms by which to explain our findings in suicide completers, we (1) assessed the role of promoter polymorphisms in determining expression in the brain and in vitro, and (2) examined CpG methylation and levels of methylated histone H3 lysine-27 in the promoter regions of these genes in the prefrontal cortex of suicide completers and healthy controls. We identified several promoter haplotypes in SMS and SMOX, but found no consistent effects of haplotype on expression levels in either the brain or in reporter gene assays performed in three different cell lines. We also found no overall effects of epigenetic factors in determining expression, with the exception of a relationship between CpG methylation at one site in the promoter of SMOX and its expression in Brodmann area 8/9. In conclusion, the genetic and epigenetic factors examined in this study show little influence on the expression levels of SMS and SMOX, and do not appear to be responsible for the dysregulated expression of these genes in suicide completers.
精胺合成酶（SMS）和精脒氧化酶（SMOX）水平的改变，这两种酶参与多胺代谢，先前在自杀完成者的大脑中观察到。为了描述遗传和表观遗传因素在决定这些基因表达水平中的作用，以及确定解释自杀完成者中我们发现的潜在机制，我们（1）评估了启动子多态性在决定大脑和体外表达中的作用，以及（2）在自杀完成者和健康对照者的前额叶皮层中检查了这些基因启动子区域的 CpG 甲基化和甲基化组蛋白 H3 赖氨酸-27 水平。我们在 SMS 和 SMOX 中鉴定了几个启动子单倍型，但在大脑或在三种不同细胞系中进行的报告基因测定中，没有发现单倍型对表达水平的一致影响。我们还没有发现表观遗传因素在决定表达方面的总体影响，除了 SMOX 启动子中一个位点的 CpG 甲基化与其在布罗德曼区 8/9 的表达之间存在关系。总之，本研究中检查的遗传和表观遗传因素对 SMS 和 SMOX 的表达水平影响很小，并且似乎不是这些基因在自杀完成者中失调表达的原因。
