Association analysis of GABA(A) beta 2 and gamma 2 gene polymorphisms withevent-related prefrontal activity in man

Gamma-aminobutyric acid (GABA)(A)-receptors play a crucial role in the gene ration of electroencephalogram (EEC) oscillations and evoked potentials (ER Ps). The present association study was designed to test whether EEG and ERP s are modulated by genetic variations of the human GABA(A) beta2 (GABRB2) a nd gamma2 (GABRG2) genes on chromosome 5q33. The genotypes of two nucleotid e substitution polymorphisms of the GABRB2 and GABRG2 genes were assessed i n 95 psychiatrically healthy subjects of German descent. Neurophysiological phenotyping was performed with four factorized EEG/ERP parameters: EEG act ivation, anterior and posterior EEG synchronization, and event-related acti vity (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 GA BRG2 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 ev en 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 thre e-dimensional neuroanatomic Talairach space-time showed a reduction in the event-related signal power after 120 ms in the right dorsolateral prefronta l cortex. Taking into account the risk of false-positive association findin gs attributable to multiple testing, our results encourage further replicat ion studies to examine the phenotype-genotype relationship of GABRG2 gene v ariants and event-related prefrontal activity.