Okamura Kenji, Shirakawa Osamu, Nishiguchi Naoki, Ono Hisae, Nushida Hideyuki, Ueno Yasuhiro, Maeda Kiyoshi
Division of Psychiatry and Neurology, Faculty of Medical Sciences, Kobe University Graduate School of Medicine, Kobe, Japan.
Psychiatry Clin Neurosci. 2005 Jun;59(3):345-9. doi: 10.1111/j.1440-1819.2005.01380.x.
An association between serotonergic dysfunction in the brain and suicidal behavior has previously been suggested. The high affinity of some antipsychotic and antidepressant drugs to serotonin 6 (5-HT6) receptors, and the predominant localization of 5-HT6 receptors in some limbic regions, suggest that 5-HT6 receptors play a role in the pathogenesis of suicide. The objective of the present study was to examine the association between suicide victims and two polymorphisms of the 5-HT6 receptor gene: a biallelic polymorphism (267C/T) in exon 1 and a trinucleotide repeat polymorphism (GCC) in the 5'-upstream region of the gene. The two polymorphisms were genotyped in 163 suicide victims and 166 controls, and the distribution of genotype and allele frequencies between the two groups were compared. Haplotype frequencies of these two polymorphisms were estimated from genotypic data by the maximum-likelihood method. In both polymorphisms, there were no significant differences in genotype or allele frequencies between the suicide victims and the controls. Moreover, there were no significant differences in the haplotype distributions of these polymorphisms between the two groups. These findings suggest that it is unlikely that the 5-HT6 receptor gene is involved in the susceptibility to suicide.
此前已有研究表明大脑中血清素功能障碍与自杀行为之间存在关联。一些抗精神病药物和抗抑郁药物对血清素6(5-HT6)受体具有高亲和力,且5-HT6受体主要定位于某些边缘区域,这表明5-HT6受体在自杀发病机制中发挥作用。本研究的目的是检验自杀受害者与5-HT6受体基因的两种多态性之间的关联:外显子1中的双等位基因多态性(267C/T)以及该基因5'上游区域的三核苷酸重复多态性(GCC)。对163名自杀受害者和166名对照者进行了这两种多态性的基因分型,并比较了两组之间基因型和等位基因频率的分布。通过最大似然法从基因型数据估计这两种多态性的单倍型频率。在这两种多态性中,自杀受害者与对照者之间的基因型或等位基因频率均无显著差异。此外,两组之间这些多态性的单倍型分布也无显著差异。这些发现表明5-HT6受体基因不太可能参与自杀易感性。