Suicide candidate genes associated with bipolar disorder and schizophrenia: an exploratory gene expression profiling analysis of post-mortem prefrontal cortex.
Suicide candidate genes associated with bipolar disorder and schizophrenia: an exploratory gene expression profiling analysis of post-mortem prefrontal cortex.
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DOI：
10.1186/1471-2164-8-413
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发表时间：
2007-11-12
期刊：
影响因子：
4.4
通讯作者：
Gershenfeld, Howard K
中科院分区：
文献类型：
--
作者：
Kim, Sanghyeon;Choi, Kwong-Ho;Baykiz, Ali Fuat;Gershenfeld, Howard K
自杀是病因不明的严重精神障碍的一个重要和潜在的可预防的后果。基因表达谱分析技术提供了一个公正的方法来确定候选基因的精神障碍。使用死后前额叶皮层（Brodmann's Area 46/10）组织的微阵列研究需要更大的样本量。这项研究提出了一个问题：自杀的差异表达基因在多大程度上是一组诊断特异性基因（双相情感障碍与精神分裂症），而不是一个共享的共同途径？在一个大的Affyandroid人类基因组U133 A微阵列数据集的再分析中，在诊断组内自杀完成者与非自杀组之间比较基因表达水平，即双相情感障碍（N = 45; 22自杀完成者; 23非自杀）或精神分裂症（N = 45; 10自杀完成者; 35非自杀）。在双相情感障碍患者中，发现了13个基因，在精神分裂症患者中，发现了70个基因的差异表达。两个基因，PLSCR 4（磷脂scramblase 4）和EMX 2（空气门同源物2（果蝇））的差异表达在两个诊断组的自杀组通过微阵列分析。通过qRT-PCR，PLSCR 4和EMX 2在精神分裂症自杀完成者中显著下调，但在双相情感障碍中无法证实。这种分子水平的分析表明，诊断特异性基因占主导地位的自杀与非自杀群体之间的共同共有的基因。这些差异表达的候选基因是自杀的神经相关基因，不一定是因果关系。虽然自杀是一个具有许多途径的复杂终点，但这些候选基因为未来的分子机制研究和遗传关联研究提供了切入点，以测试因果关系。
Suicide is an important and potentially preventable consequence of serious mental disorders of unknown etiology. Gene expression profiling technology provides an unbiased approach to identifying candidate genes for mental disorders. Microarray studies with post-mortem prefrontal cortex (Brodmann's Area 46/10) tissue require larger sample sizes. This study poses the question: to what extent are differentially expressed genes for suicide a diagnostic specific set of genes (bipolar disorder vs. schizophrenia) vs. a shared common pathway? In a reanalysis of a large set of Affymetrix Human Genome U133A microarray data, gene expression levels were compared between suicide completers vs. non-suicide groups within a diagnostic group, namely Bipolar disorder (N = 45; 22 suicide completers; 23 non-suicide) or Schizophrenia (N = 45; 10 suicide completers ; 35 non-suicide). Among bipolar samples, 13 genes were found and among schizophrenia samples, 70 genes were found as differentially expressed. Two genes, PLSCR4 (phospholipid scramblase 4) and EMX2 (empty spiracles homolog 2 (Drosophila)) were differentially expressed in suicide groups of both diagnostic groups by microarray analysis. By qRT-PCR, PLSCR4 and EMX2 were significantly down-regulated in the schizophrenia suicide completers, but could not be confirmed in bipolar disorder. This molecular level analysis suggests that diagnostic specific genes predominate to shared genes in common among suicide vs. non-suicide groups. These differentially expressed, candidate genes are neural correlates of suicide, not necessarily causal. While suicide is a complex endpoint with many pathways, these candidate genes provide entry points for future studies of molecular mechanisms and genetic association studies to test causality.