Must Anne, Tasa Gunnar, Lang Aavo, Vasar Eero, Kõks Sulev, Maron Eduard, Väli Marika
Institute of Physiology, Tartu University, Ravila 19, Tartu 50411, Estonia.
BMC Med Genet. 2008 Apr 23;9:34. doi: 10.1186/1471-2350-9-34.
Neuroimaging studies have demonstrated volumetric abnormalities in limbic structures of suicide victims. The morphological changes might be caused by some inherited neurodevelopmental defect, such as failure to form proper axonal connections due to genetically determined dysfunction of neurite guidance molecules. Limbic system-associated membrane protein (LSAMP) is a neuronal adhesive molecule, preferentially expressed in developing limbic system neuronal dendrites and somata. Some evidence for the association between LSAMP gene and behavior has come from both animal as well as human studies but further investigation is required. In current study, polymorphic loci in human LSAMP gene were examined in order to reveal any associations between genetic variation in LSAMP and suicidal behaviour.
DNA was obtained from 288 male suicide victims and 327 healthy male volunteers. Thirty SNPs from LSAMP gene and adjacent region were selected by Tagger algorithm implemented in Haploview 3.32. Genotyping was performed using the SNPlex (Applied Biosystems) platform. Data was analyzed by Genemapper 3.7, Haploview 3.32 and SPSS 13.0.
Chi square test revealed four allelic variants (rs2918215, rs2918213, rs9874470 and rs4821129) located in the intronic region of the gene to be associated with suicide, major alleles being overrepresented in suicide group. However, the associations did not survive multiple correction test. Defining the haplotype blocks using confidence interval algorithm implemented in Haploview 3.32, we failed to detect any associated haplotypes.
Despite a considerable amount of investigation on the nature of suicidal behaviour, its aetiology and pathogenesis remain unknown. This study examined the variability in LSAMP gene in relation to completed suicide. Our results indicate that LSAMP might play a role in pathoaetiology of suicidal behaviour but further studies are needed to understand its exact contribution.
神经影像学研究已证实自杀受害者边缘系统结构存在体积异常。这些形态变化可能由某些遗传性神经发育缺陷引起,例如由于神经突导向分子的基因决定性功能障碍导致无法形成适当的轴突连接。边缘系统相关膜蛋白(LSAMP)是一种神经元黏附分子,优先表达于发育中的边缘系统神经元树突和胞体。来自动物和人类研究的一些证据表明LSAMP基因与行为之间存在关联,但仍需进一步研究。在本研究中,对人类LSAMP基因的多态性位点进行了检测,以揭示LSAMP基因变异与自杀行为之间的任何关联。
从288名男性自杀受害者和327名健康男性志愿者中获取DNA。通过Haploview 3.32中实现的Tagger算法从LSAMP基因及其相邻区域选择了30个单核苷酸多态性(SNP)。使用SNPlex(应用生物系统公司)平台进行基因分型。数据通过Genemapper 3.7、Haploview 3.32和SPSS 13.0进行分析。
卡方检验显示位于该基因内含子区域的四个等位基因变体(rs2918215、rs2918213、rs9874470和rs4821129)与自杀相关,主要等位基因在自杀组中过度表达。然而,这些关联在多重校正检验后未成立。使用Haploview 3.32中实现的置信区间算法定义单倍型块时,我们未检测到任何相关单倍型。
尽管对自杀行为的本质进行了大量研究,但其病因和发病机制仍然未知。本研究检查了与自杀完成相关的LSAMP基因的变异性。我们的结果表明LSAMP可能在自杀行为的病理病因中起作用,但需要进一步研究以了解其确切作用。