The Interactive Effect of Genetic and Epigenetic Variations in and Genes on Anxiety and Brain EEG Parameters.

is a key stress-responsive regulator of the hypothalamic-pituitary-adrenal axis. To elucidate the contribution of rs1360780 C/T alleles to aging and longevity, we genotyped in a cohort of 800 non-demented and Alzheimer's disease (AD) subjects of different age, taking into account the allele state of ε4, the major risk factor for AD. Furthermore, we searched for the association of with subcohorts of non-demented subjects evaluated for anxiety and resting-state quantitative EEG characteristics, associated with cognitive, emotional, and functional brain activities. We observed that increased state anxiety scores depend on the combination of the and genotypes and on the DNA methylation state of the promoter and genotype. We also found a significant gender-dependent correlation between promoter methylation and alpha-, delta-, and theta-rhythms. Analysis of the expression in an independent cohort revealed a significant upregulation of in females versus males. Our data suggest a synergistic effect of the stress-associated () and neurodegeneration-associated () gene alleles on anxiety and the gender-dependent effect of on neurophysiological brain activity.