Hohoff Christa, Weber Heike, Richter Jan, Domschke Katharina, Zwanzger Peter M, Ohrmann Patricia, Bauer Jochen, Suslow Thomas, Kugel Harald, Baumann Christian, Klauke Benedikt, Jacob Christian P, Fritze Jürgen, Bandelow Borwin, Gloster Andrew T, Gerlach Alexander L, Kircher Tilo, Lang Thomas, Alpers Georg W, Ströhle Andreas, Fehm Lydia, Wittchen Hans-Ulrich, Arolt Volker, Pauli Paul, Hamm Alfons, Reif Andreas, Deckert Jürgen
Department of Psychiatry and Psychotherapy, University of Muenster, Muenster, Germany.
Am J Med Genet B Neuropsychiatr Genet. 2015 Apr;168B(3):211-22. doi: 10.1002/ajmg.b.32299. Epub 2015 Mar 4.
Accumulating evidence from mouse models points to the G protein-coupled receptor RGS2 (regulator of G-protein signaling 2) as a promising candidate gene for anxiety in humans. Recently, RGS2 polymorphisms were found to be associated with various anxiety disorders, e.g., rs4606 with panic disorder (PD), but other findings have been negative or inconsistent concerning the respective risk allele. To further examine the role of RGS2 polymorphisms in the pathogenesis of PD, we genotyped rs4606 and five additional RGS2 tag single nucleotide polymorphisms (SNPs; rs16834831, rs10801153, rs16829458, rs1342809, rs1890397) in two independent PD samples, comprising 531 matched case/control pairs. The functional SNP rs4606 was nominally associated with PD when both samples were combined. The upstream SNP rs10801153 displayed a Bonferroni-resistant significant association with PD in the second and the combined sample (P = 0.006 and P = 0.017). We furthermore investigated the effect of rs10801153 on dimensional anxiety traits, a behavioral avoidance test (BAT), and an index for emotional processing in the respective subsets of the total sample. In line with categorical results, homozygous risk (G) allele carriers displayed higher scores on the Agoraphobic Cognitions Questionnaire (ACQ; P = 0.015) and showed significantly more defensive behavior during fear provoking situations (P = 0.001). Furthermore, significant effects on brain activation in response to angry (P = 0.013), happy (P = 0.042) and neutral faces (P = 0.032) were detected. Taken together, these findings provide further evidence for the potential role of RGS2 as a candidate gene for PD.
来自小鼠模型的越来越多的证据表明，G蛋白偶联受体RGS2（G蛋白信号调节因子2）是人类焦虑症一个很有前景的候选基因。最近，人们发现RGS2基因多态性与各种焦虑症有关，例如，rs4606与惊恐障碍（PD）有关，但关于各自的风险等位基因，其他研究结果为阴性或不一致。为了进一步研究RGS2基因多态性在PD发病机制中的作用，我们对两个独立的PD样本中的rs4606和另外五个RGS2标签单核苷酸多态性（SNP；rs16834831、rs10801153、rs16829458、rs1342809、rs1890397）进行了基因分型，这两个样本包括531对匹配的病例/对照。当两个样本合并时，功能性SNP rs4606与PD存在名义上的关联。上游SNP rs10801153在第二个样本和合并样本中与PD显示出经Bonferroni校正后的显著关联（P = 0.006和P = 0.017）。我们还研究了rs10801153对维度焦虑特质、行为回避测试（BAT）以及总样本各子集中情绪加工指标的影响。与分类结果一致，纯合风险（G）等位基因携带者在广场恐惧认知问卷（ACQ；P = 0.015）上得分更高，并且在恐惧诱发情境中表现出明显更多的防御行为（P = 0.001）。此外，检测到对愤怒（P = 0.013）、快乐（P = 0.042）和中性面孔（P = 0.032）的脑激活有显著影响。综上所述，这些发现为RGS2作为PD候选基因的潜在作用提供了进一步的证据。
