Department of Psychiatry, Chonnam National University Medical School, Gwangju, Korea.
King's College London, Institute of Psychiatry, Psychology and Neuroscience, London, United Kingdom.
Sci Rep. 2020 Mar 26;10(1):5519. doi: 10.1038/s41598-020-62449-2.
High levels of methylation in the GR gene (nuclear receptor subfamily 3, group C, member 1; NR3C1) have been associated with depression and cardiovascular risk. This study aimed to investigate whether NR3C1 methylation status was associated with the long-term prognosis of acute coronary syndrome (ACS) considering depression and cardiovascular status at the early phase of ACS. A total of 969 patients with recent ACS were recruited at a tertiary university hospital in Korea. Baseline evaluations were made from 2007 to 2012, including DSM-IV depressive disorder, NR3C1 methylation, and various demographic and clinical characteristics such as cardiovascular risk markers. Over a 5~12 year follow-up after the index ACS, time to major adverse cardiac event (MACE) was investigated using Cox regression models. Higher NR3C1 methylation status was associated with depression and several cardiovascular risk markers at baseline. NR3C1 hypermethylation predicted worse long-term prognosis of ACS only in the presence of depressive disorder with significant synergistic interaction terms and independent of potential confounding factors. Synergistic effects of depressive disorder and NR3C1 hypermethylation on long-term cardiac outcomes in ACS were found. NR3C1 methylation status represents a candidate prognostic biomarker for ACS in combination with a diagnosis of depressive disorder. Further research is needed to ascertain the generalisability of these findings.
GR 基因（核受体亚家族 3，C 组，成员 1；NR3C1）的高甲基化水平与抑郁和心血管风险有关。本研究旨在探讨 NR3C1 甲基化状态是否与急性冠状动脉综合征（ACS）的长期预后相关，同时考虑 ACS 早期的抑郁和心血管状况。韩国一家三级大学医院共招募了 969 名近期 ACS 患者。基线评估于 2007 年至 2012 年进行，包括 DSM-IV 抑郁障碍、NR3C1 甲基化以及心血管风险标志物等各种人口统计学和临床特征。在 ACS 后的 5~12 年随访期间，使用 Cox 回归模型调查主要不良心脏事件（MACE）的时间。较高的 NR3C1 甲基化状态与基线时的抑郁和几种心血管风险标志物有关。只有在存在抑郁障碍的情况下，NR3C1 高甲基化才预示着 ACS 的长期预后较差，且具有显著的协同交互作用，并独立于潜在的混杂因素。抑郁障碍和 NR3C1 高甲基化对 ACS 长期心脏结局的协同作用。NR3C1 甲基化状态与抑郁障碍的诊断相结合，代表 ACS 的候选预后生物标志物。需要进一步的研究来确定这些发现的普遍性。
