Abstract:
Delirium is risky and indicates poor outcomes for patients. Therefore, it is crucial to create an effective delirium detection method. However, the epigenetic pathophysiology of delirium remains largely unknown. We aimed to discover reliable and replicable epigenetic (DNA methylation: DNAm) markers that are associated with delirium including post-operative delirium (POD) in blood obtained from patients among four independent cohorts. Blood DNA from four independent cohorts (two inpatient cohorts and two surgery cohorts; 16 to 88 patients each) were analyzed using the Illumina EPIC array platform for genome-wide DNAm analysis. We examined DNAm differences in blood between patients with and without delirium including POD. When we compared top CpG sites previously identified from the initial inpatient cohort with three additional cohorts (one inpatient and two surgery cohorts), 11 of the top 13 CpG sites showed statistically significant differences in DNAm values between the delirium group and non-delirium group in the same directions as found in the initial cohort. This study demonstrated the potential value of epigenetic biomarkers as future diagnostic tools. Furthermore, our findings provide additional evidence of the potential role of epigenetics in the pathophysiology of delirium including POD.
摘要:
谵妄是有风险的,表明患者的预后较差。因此,建立有效的谵妄检测方法至关重要。然而,谵妄的表观遗传病理生理学在很大程度上仍然未知。我们旨在发现与谵妄相关的可靠且可复制的表观遗传(DNA甲基化:DNAm)标记,包括四个独立队列中患者血液中的术后谵妄(POD)。使用IlluminaEPIC阵列平台分析来自四个独立队列(两个住院队列和两个手术队列;每个16至88名患者)的血液DNA用于全基因组DNAm分析。我们检查了有和没有包括POD在内的谵妄患者血液中DNAm的差异。当我们将先前从初始住院患者队列中确定的最高CpG位点与另外三个队列(一个住院患者和两个手术队列)进行比较时,前13个CpG位点中的11个在谵妄组和非谵妄组之间的DNAm值在与初始队列相同的方向上显示出统计学上的显着差异。这项研究证明了表观遗传生物标志物作为未来诊断工具的潜在价值。此外,我们的研究结果为表观遗传学在包括POD在内的谵妄的病理生理学中的潜在作用提供了额外的证据.