Mouri Kentaro, Hishimoto Akitoyo, Fukutake Masaaki, Nishiguchi Naoki, Shirakawa Osamu, Maeda Kiyoshi
Department of Psychiatry, Kobe University Graduate School of Medicine, Kobe, Japan.
Kobe J Med Sci. 2010 Apr 8;55(5):E116-21.
Genetic factors for panic disorder have been consistently observed in family and twin studies. Regulators of G-protein signaling (RGS) is a family of proteins that negatively regulate the intracellular signaling of G protein-coupled receptors such as dopamine and serotonin receptors. RGS2, one of the RGS families, has been suggested to plays a role in anxiety and/or aggressive behavior. Polymorphisms in the RGS2 gene were recently associated with panic disorder, trait anxiety, suicidal behavior, and generalized anxiety disorder. From these findings, we tried to replicate an association between panic disorder and genetic variations of the RGS2 using a case-control study of 186 patients with panic disorder and 380 controls in Japanese. We genotyped five common single nucleotide polymorphisms (SNPs) by the PCR-RFLP method and the TaqMan Assays. Neither genotype distribution nor allele frequency for five SNPs was significant different between the panic disorder and control groups. We found a relative tight LD block in the 5'- flanking region of RGS2 gene. One of the common haplotypes, AC of rs2746071 and rs2746072, has shown a nominally significant association with panic disorder (p=0.027). This significance, however, did not remain after correction for multiple testing. These findings suggest that RGS2 may not be genetically involved in the biological susceptibility to panic disorder in Japanese.
在家族和双胞胎研究中一直观察到惊恐障碍的遗传因素。G蛋白信号调节因子（RGS）是一类蛋白质家族，可负向调节G蛋白偶联受体（如多巴胺和5-羟色胺受体）的细胞内信号传导。RGS家族之一的RGS2已被认为在焦虑和/或攻击行为中起作用。RGS2基因的多态性最近与惊恐障碍、特质焦虑、自杀行为和广泛性焦虑障碍相关。基于这些发现，我们试图通过一项针对186例日本惊恐障碍患者和380例对照的病例对照研究，来复制惊恐障碍与RGS2基因变异之间的关联。我们采用PCR-RFLP方法和TaqMan检测法对五个常见单核苷酸多态性（SNP）进行基因分型。惊恐障碍组和对照组之间五个SNP的基因型分布和等位基因频率均无显著差异。我们在RGS2基因的5'侧翼区域发现了一个相对紧密的连锁不平衡（LD）区域。常见单倍型之一，即rs2746071和rs2746072的AC，与惊恐障碍显示出名义上的显著关联（p = 0.027）。然而，在进行多重检验校正后，这种显著性不再存在。这些发现表明，在日本人中，RGS2可能在遗传上不参与惊恐障碍的生物学易感性。
