Winterer G, Smolka M, Samochowiec J, Mulert C, Ziller M, Mahlberg R, Wuebben Y, Gallinat J, Rommelspacher H, Herrman W M, Sander T
Department of Psychiatry, University Hospital Benjamin Franklin, Free University of Berlin, Germany.
Hum Genet. 2000 Nov;107(5):513-8. doi: 10.1007/s004390000401.
Gamma-aminobutyric acid (GABA)A-receptors play a crucial role in the generation of electroencephalogram (EEG) oscillations and evoked potentials (ERPs). The present association study was designed to test whether EEG and ERPs are modulated by genetic variations of the human GABAA beta2 (GABRB2) and gamma2 (GABRG2) genes on chromosome 5q33. The genotypes of two nucleotide substitution polymorphisms of the GABRB2 and GABRG2 genes were assessed in 95 psychiatrically healthy subjects of German descent. Neurophysiological phenotyping was performed with four factorized EEG/ERP parameters: EEG activation, anterior and posterior EEG synchronization, and event-related activity (N100/ P200-complex). No genotypic association was found for the GABRB2 nucleotide exchange polymorphism with any electrophysiological parameter. A significant association was found between the genotype of the intronic GABRG2 G-->A nucleotide exchange and the event-related N100/P200 (ANOVA: F=3.81; df=2; P=0.026). A comparison of homozygous subjects carrying either the G/G or A/A genotype of the GABRG2 polymorphism consistently revealed an even stronger difference in the effect-size (ANOVA: F=11.13; df=1; P=0.002). Post hoc analysis of this association with current density analysis in three-dimensional neuroanatomic Talairach space-time showed a reduction in the event-related signal power after 120 ms in the right dorsolateral prefrontal cortex. Taking into account the risk of false-positive association findings attributable to multiple testing, our results encourage further replication studies to examine the phenotype-genotype relationship of GABRG2 gene variants and event-related prefrontal activity.
γ-氨基丁酸（GABA）A受体在脑电图（EEG）振荡和诱发电位（ERP）的产生中起关键作用。本关联研究旨在测试EEG和ERP是否受5号染色体q33上人类GABAAβ2（GABRB2）和γ2（GABRG2）基因的遗传变异调节。在95名德国血统的精神健康受试者中评估了GABRB2和GABRG2基因的两个核苷酸替代多态性的基因型。使用四个分解的EEG/ERP参数进行神经生理表型分析：EEG激活、前后EEG同步以及事件相关活动（N100/P200复合波）。未发现GABRB2核苷酸交换多态性与任何电生理参数存在基因型关联。发现内含子GABRG2基因G→A核苷酸交换的基因型与事件相关的N100/P200之间存在显著关联（方差分析：F = 3.81；自由度 = 2；P = 0.026）。对携带GABRG2多态性G/G或A/A基因型的纯合受试者进行比较，始终显示效应大小存在更强差异（方差分析：F = 11.13；自由度 = 1；P = 0.002）。在三维神经解剖Talairach时空对该关联与电流密度分析进行事后分析，结果显示在右背外侧前额叶皮质中，120毫秒后事件相关信号功率降低。考虑到多重检验可能导致的假阳性关联结果风险，我们的结果鼓励进一步开展重复研究，以检验GABRG2基因变异与事件相关前额叶活动的表型-基因型关系。
