Genetic and Epigenetic Analysis of SSAT Gene Dysregulation in Suicidal Behavior
Genetic and Epigenetic Analysis of SSAT Gene Dysregulation in Suicidal Behavior
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DOI：
10.1002/ajmg.b.30901
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发表时间：
2009-09-05
影响因子：
2.8
通讯作者：
Malafosse, Alain
中科院分区：
文献类型：
--
作者：
Guipponi, Michel;Deutsch, Samuel;Malafosse, Alain
最近有人提出SSAT基因在自杀倾向中起作用。在自杀未遂者的大脑中发现SSAT表达下调。此外，单核苷酸多态性（SNP） rs6526342与SSA T表达变异和自杀行为有关。在本研究中，我们旨在描述SSAT失调与自杀行为之间的关系。为此，我们测量了自杀完成者（n = 20）和对照组（n = 20）的腹侧前额叶皮层（VPFC）的SSAT表达水平，发现自杀受害者的SSAT表达水平显著下调（P = 0.007）。为了确定SSAT表达调控的基础，我们对来自CEPH收集的53个淋巴母细胞样细胞系的309个snp与SSAT转录水平进行了关联分析。然后，我们检查了SSAT启动子区的甲基化状态，在男性和女性自杀完成者和对照组中，他们的SSAT大脑表达已经被测量。我们没有发现任何证据支持snp在控制SSAT表达水平方面的作用。SSAT启动子甲基化水平在自杀完成者和对照组之间没有差异，也与SSAT表达水平无关。此外，我们没有发现自杀行为与SSAT基因内的snp之间存在遗传关联的迹象。我们的研究提供了新的结果，表明SSAT表达失调确实在自杀行为中起作用。然而，我们的数据不支持rs6526342与SSAT表达变异或自杀行为之间的任何关联。(C) 2008 Wiley-Liss, Inc。
It has recently been proposed that the SSAT gene plays a role in the predisposition to suicidal behavior. SSAT expression was found to be down-regulated in the brain of suicide completers. In addition, a single nucleotide polymorphism (SNP) rs6526342 was associated both with variation in SSA T expression and with suicidal behavior. In this study, we aimed to characterize the relationship between SSAT dysregulation and suicide behavior. To this end, we measured SSAT expression levels in the ventral prefrontal cortex (VPFC) of suicide completers (n = 20) and controls (n = 20) and found them to be significantly down-regulated in suicide victims (P = 0.007). To identify the basis of the regulation of SSAT expression, we performed an association analysis of 309 SNPs with SSAT transcript levels in 53 lymphoblastoid cell lines from the CEPH collection. We then examined the methylation status of the SSAT promoter region in males and females suicide completers and control subjects whose SSAT brain expression had been measured. We found no evidence to support a role for SNPs in controlling the level of SSAT expression. SSAT promoter methylation levels were not different between suicide completers and controls and did not correlate with SSAT expression levels. In addition, we found no indication of a genetic association between suicidal behavior and SNPs located within the SSAT gene. Our study provides new results which show that dysregulation of SSAT expression does play a role in suicide behavior. However, our data do not support any association between rs6526342 and variation in SSAT expression or suicidal behavior. (C) 2008 Wiley-Liss, Inc.