Cui Huxing, Nishiguchi Naoki, Ivleva Elena, Yanagi Masaya, Fukutake Masaaki, Nushida Hideyuki, Ueno Yasuhiro, Kitamura Noboru, Maeda Kiyoshi, Shirakawa Osamu
Department of Psychiatry and Neurology, Kobe University Graduate School of Medicine, Kobe, Japan.
Neuropsychopharmacology. 2008 Jun;33(7):1537-44. doi: 10.1038/sj.npp.1301557. Epub 2007 Aug 29.
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.
G蛋白信号调节因子是一类蛋白质，它们对G蛋白偶联受体（如血清素受体）的细胞内信号传导起负调节作用。最近的研究表明，这些蛋白质之一，即G蛋白信号调节因子2（RGS2），在焦虑和/或攻击行为中起重要作用。为了探讨RGS2基因与自杀易感性的关系，我们对日本自杀受害者的RGS2基因序列变异进行了筛查，并对RGS2基因多态性与自杀受害者进行了关联研究。在通过突变筛查鉴定出的8种多态性中，我们对RGS2基因中的4种常见单核苷酸多态性（SNP）进行了基因分型，发现SNP3（C+2971G，rs4606）的基因型分布以及SNP2（C-395G，rs2746072）和SNP3的等位基因在自杀身亡者与对照组之间存在显著差异。两组之间单倍型的分布也有显著差异（总体p<0.0001）。此外，自杀受试者死后大脑的杏仁核和前额叶皮质（布罗德曼9区（BA9））中RGS2免疫反应性显著增加。这些发现表明，RGS2在日本人群自杀的生物学易感性中存在遗传关联。
