Association of RGS2 gene Polymorphisms with suicide and increased RGS2 immunoreactivity in the postmortem brain of suicide victims
Association of RGS2 gene Polymorphisms with suicide and increased RGS2 immunoreactivity in the postmortem brain of suicide victims
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DOI：
10.1038/sj.npp.1301557
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发表时间：
2008-06-01
影响因子：
7.6
通讯作者：
Shirakawa, Osamu
中科院分区：
文献类型：
--
作者：
Cui, Huxing;Nishiguchi, Naoki;Shirakawa, Osamu
G蛋白信号传导调节因子是负调节G蛋白偶联受体（如血清素受体）的细胞内信号传导的蛋白质家族。最近的研究表明，这些蛋白质之一，G蛋白信号传导调节器2（RGS 2），在焦虑和/或攻击行为中起着重要作用。为了探讨RGS 2基因在自杀易感性中的参与，我们筛选了日本自杀受害者的RGS 2基因序列变异，并进行了RGS 2基因多态性与自杀受害者的关联研究。在通过突变筛查确定的8种多态性中，我们对RGS 2基因中4种常见的单核苷酸多态性（SNP）进行了基因分型，发现SNP 3（C +2971 G，rs 4606）基因型和SNP 2（C-395 G，rs 2746072）和SNP 3的等位基因在自杀未遂者和对照组之间的分布存在显著差异。单倍型的分布在两组之间也有显著差异（总体p < 0.0001）。此外，RGS 2免疫反应显着增加杏仁核和前额叶皮层（布罗德曼区9（BA 9））的自杀受试者的死后大脑。这些发现表明，RGS 2基因与日本人群自杀的生物易感性有关。
Regulators of G-protein signaling are a family of proteins that negatively regulate the intracellular signaling of G protein-coupled receptors, such as the serotonin receptor. Recent studies have suggested that one of these proteins, the regulator of G-protein signaling 2 (RGS2), plays an important part in anxiety and/or aggressive behavior. To explore the involvement of the RGS2 gene in the vulnerability to suicide, we screened Japanese suicide victims for sequence variations in the RGS2 gene and carried out an association study of RGS2 gene polymorphisms with suicide victims. In the eight identified polymorphisms that were identified by mutation screening, we genotyped four common single-nucleotide polymorphisms (SNPs) in the RGS2 gene, and found significant differences in the distribution of the SNP3 (C + 2971G, rs4606) genotypes and alleles of the SNP2 (C-395G, rs2746072) and the SNP3 between completed suicides and the controls. The distribution of the haplotype was also significantly different between the two groups (global p < 0.0001). Furthermore, RGS2 immunoreactivity significantly increased in the amygdala and the prefrontal cortex (Brodmann area 9 (BA9)) of the postmortem brain of the suicide subjects. These findings suggest that RGS2 is genetically involved in the biological susceptibility to suicide in the Japanese population.