Longitudinal profiling in patients undergoing cardiac surgery reveals postoperative changes in DNA methylation.
Longitudinal profiling in patients undergoing cardiac surgery reveals postoperative changes in DNA methylation.
复制标题
DOI：
10.1186/s13148-022-01414-4
复制
发表时间：
2022-12-30
影响因子：
5.7
通讯作者：
中科院分区：
文献类型：
--
作者：
心脏手术和心肺转流术诱导大量的免疫和炎症反应，其过度激活与显著的肺、心血管和神经系统并发症相关。与免疫和炎症反应相对应的是心脏和血管系统本身的变化，这些变化通过尚不清楚的机制共同驱动术后并发症。纵向DNA甲基化分析有可能识别继发于手术的基因调控机制的变化，并识别预测和/或引起术后并发症的分子过程。在这项研究中，我们测量了96例接受体外循环心脏手术的患者术前和术后全血样本中的DNA甲基化。 虽然绝大多数DNA甲基化在考虑细胞类型组成的变化后没有变化，但我们确定了几个甲基化具有统计学显著性术后变化的位点。此外，这些位点中的两个与新发术后房颤相关，这是心脏手术后的重要并发症。配对的统计分析，使用流式细胞仪数据来支持对细胞类型异质性的充分控制，以及对患者亚组中IL 6水平的测量增加了该分析的严谨性，使我们能够区分细胞类型变异性与甲基化的实际变化。 这项研究确定了心脏手术后立即发生的DNA甲基化的显着变化，并表明这些DNA甲基化的急性变化具有识别与主要术后并发症相关的过程的粒度。这项研究还建立了控制大型人类队列中细胞类型变异性的方法，这可能有助于在急性和慢性疾病背景下进行表观遗传标记的其他纵向研究。 在线版本包含补充材料，可通过10.1186/s13148-022-01414-4获得。
Cardiac surgery and cardiopulmonary bypass induce a substantial immune and inflammatory response, the overactivation of which is associated with significant pulmonary, cardiovascular, and neurologic complications. Commensurate with the immune and inflammatory response are changes in the heart and vasculature itself, which together drive postoperative complications through mechanisms that are poorly understood. Longitudinal DNA methylation profiling has the potential to identify changes in gene regulatory mechanisms that are secondary to surgery and to identify molecular processes that predict and/or cause postoperative complications. In this study, we measure DNA methylation in preoperative and postoperative whole blood samples from 96 patients undergoing cardiac surgery on cardiopulmonary bypass. While the vast majority of DNA methylation is unchanged by surgery after accounting for changes in cell-type composition, we identify several loci with statistically significant postoperative changes in methylation. Additionally, two of these loci are associated with new-onset postoperative atrial fibrillation, a significant complication after cardiac surgery. Paired statistical analysis, use of FACS data to support sufficient control of cell-type heterogeneity, and measurement of IL6 levels in a subset of patients add rigor to this analysis, allowing us to distinguish cell-type variability from actual changes in methylation. This study identifies significant changes in DNA methylation that occur immediately after cardiac surgery and demonstrates that these acute alterations in DNA methylation have the granularity to identify processes associated with major postoperative complications. This research also establishes methods for controlling for cell-type variability in a large human cohort that may be useful to deploy in other longitudinal studies of epigenetic marks in the setting of acute and chronic disease. The online version contains supplementary material available at 10.1186/s13148-022-01414-4.
登录
查看更多内容
影响因子：
12.3
作者：
Jaffe AE;Irizarry RA
通讯作者：
Irizarry RA
影响因子：
4.8
作者：
Wang, Peng;Wu, Yanfang;Tang, Jie
通讯作者：
Tang, Jie
影响因子：
12.3
作者：
Akalin A;Kormaksson M;Li S;Garrett-Bakelman FE;Figueroa ME;Melnick A;Mason CE
通讯作者：
Mason CE
影响因子：
4.6
作者：
Hiesmayr, MJ;Spittler, A;Roth, E
通讯作者：
Roth, E
影响因子：
3.1
作者：
Jawa, Randeep S;Anillo, Sergio;Kulaylat, Mahmoud
通讯作者：
Kulaylat, Mahmoud