Hranilovic Dubravka, Stefulj Jasminka, Furac Ivana, Kubat Milovan, Balija Melita, Jernej Branimir
Laboratory of Neurochemistry and Molecular Neurobiology, Rudjer Boskovic Institute, Zagreb, Croatia.
Biol Psychiatry. 2003 Nov 1;54(9):884-9. doi: 10.1016/s0006-3223(03)00179-3.
Disturbances in serotonin (5HT) transmission are the most frequently reported neurobiological substrates of suicidal behavior. Because 5HT transporter plays a central role in the regulation of 5HT synaptic function and its gene contains two functional polymorphisms (5-HTTLPR in the promoter region and VNTR in the second intron), it represents an interesting candidate for association studies in suicidal behavior.
In this study, a possible association of 5-HTTLPR and intron 2-VNTR polymorphisms of the 5HT transporter gene with suicidal behavior was investigated in a sample of 135 suicide victims and 299 healthy control subjects of Croatian/southern Slavic origin.
There were no significant differences in 5-HTTLPR and intron 2-VNTR genotype- and allele- frequency distributions between suicide victims and healthy control subjects; however, a tendency toward an increase of 5-HTTLPR allele L and VNTR-allele 10 were observed in suicide group. Analysis of distribution of estimated haplotype frequencies revealed differences between suicide victims and control subjects, with an excess of haplotype L10 among suicide victims (p =.0112).
Our results provide modest evidence for a possible association of the 5HT transporter gene with a completed suicide. Further studies are needed to determine whether alterations in 5HTt gene expression are involved in suicidal behavior.
血清素(5HT)传递紊乱是自杀行为中最常被报道的神经生物学基础。由于5HT转运体在5HT突触功能调节中起核心作用,且其基因包含两个功能性多态性(启动子区域的5-HTTLPR和第二个内含子中的VNTR),因此它是自杀行为关联研究中一个有趣的候选基因。
在本研究中,对135名克罗地亚/南斯拉夫裔自杀受害者和299名健康对照者的样本进行了研究,探讨5HT转运体基因的5-HTTLPR和内含子2-VNTR多态性与自杀行为之间可能存在的关联。
自杀受害者与健康对照者在5-HTTLPR和内含子2-VNTR基因型及等位基因频率分布上无显著差异;然而,在自杀组中观察到5-HTTLPR等位基因L和VNTR等位基因10有增加的趋势。对估计单倍型频率分布的分析显示,自杀受害者与对照者之间存在差异,自杀受害者中L10单倍型过多(p = 0.0112)。
我们的结果为5HT转运体基因与自杀死亡可能存在关联提供了适度证据。需要进一步研究以确定5HTt基因表达的改变是否与自杀行为有关。