Aggressive behavior may have adaptive value under some environmental conditions. However, when it is extreme or improper, it may also lead to maladaptive results, seriously threatening human and social well-being. Aggressive behavior is a multifactorial disease, and the etiology is largely unknown. The stress-related hypothalamic-pituitary-adrenal (HPA) axis is a crucial system in the stress response that has emerged as a potential mechanism of aggressive behavior. The NR3C2 gene is an important regulator of the HPA axis: it is involved in regulating HPA axis activity and behavioral adaptation to stressors. Moreover, the epigenetic mechanism of DNA methylation has been suggested to mediate the development of aggressive behavior. However, the association between NR3C2 methylation and aggressive behavior has not been studied. In the present study, we assessed NR3C2 methylation (including three regions: promoter P1, exon 1α, and the sequence downstream of exon 1α) in peripheral blood DNA of adult males with aggressive behavior (n = 106) and healthy controls (n = 104). We found the NR3C2 gene to be associated with aggressive behavior, with hypermethylation detected in the entire aggressive behavior group as well as in the robbery subgroup compared to controls. In addition, analysis of methylation at 75 CpG sites revealed that some important CpG sites are associated with aggressive behavior. Our results suggest that HPA axis-related gene NR3C2 methylation is associated with aggressive behavior. These results lend support for using NR3C2 DNA methylation as a potential biomarker of aggressive behavior.

在某些环境条件下，攻击性行为可能具有适应性价值。但是，当它极端或不当时，也可能导致适应不良的结果，严重威胁人类和社会福祉。攻击性行为是一种多因素疾病，其病因在很大程度上是未知的。与压力相关的下丘脑-垂体-肾上腺 (HPA) 轴是压力反应中的一个关键系统，已成为攻击行为的潜在机制。所述NR3C2基因是HPA轴的重要调节剂：它参与调节HPA轴活性和行为适应压力源。此外，已提出 DNA 甲基化的表观遗传机制介导攻击行为的发展。然而，NR3C2之间的关联尚未研究甲基化和攻击行为。在本研究中，我们评估了具有攻击行为的成年男性 (n = 106) 和健康对照 (n = 104) 外周血 DNA 中的NR3C2甲基化（包括三个区域：启动子 P1、外显子 1α 和外显子 1α 下游的序列） ）。我们发现NR3C2基因与攻击行为相关，与对照组相比，在整个攻击行为组以及抢劫亚组中检测到高甲基化。此外，对 75 个 CpG 位点的甲基化分析表明，一些重要的 CpG 位点与攻击行为有关。我们的结果表明 HPA 轴相关基因NR3C2甲基化与攻击行为有关。这些结果支持使用NR3C2 DNA 甲基化作为攻击行为的潜在生物标志物。