Center for Genetics and Life Science, Sirius University of Science and Technology, 354349 Sochi, Russia.
Laboratory of Evolutionary Genomics, Department of Genomics and Human Genetics, Vavilov Institute of General Genetics, Russian Academy of Sciences, 119333 Moscow, Russia.
Genes (Basel). 2022 Jan 18;13(2):164. doi: 10.3390/genes13020164.
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.
是下丘脑-垂体-肾上腺轴的关键应激反应调节剂。为了阐明 rs1360780 C/T 等位基因对衰老和长寿的贡献，我们对 800 名无痴呆和阿尔茨海默病（AD）患者的不同年龄进行了 rs1360780 的基因分型，同时考虑了 AD 的主要风险因素 ε4 等位基因的状态。此外，我们还在对焦虑和静息状态定量脑电图特征进行评估的无痴呆亚组中搜索了与认知、情绪和功能大脑活动相关的与 rs1360780 的关联。我们观察到，状态焦虑评分的增加取决于 和 的基因型以及 的启动子和 基因型的 DNA 甲基化状态的组合。我们还发现，在一个独立的队列中， 启动子甲基化与 α、δ 和 θ 节律之间存在显著的性别依赖性相关性。对另一队列中 的表达分析显示，女性中 的表达明显上调，而男性中则没有。我们的数据表明，应激相关（）和神经退行性变相关（）基因等位基因对焦虑具有协同作用，而 对神经生理大脑活动的性别依赖性影响。
