Section of Forensic Genetics, Department of Forensic Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, DK-1353 Copenhagen, Denmark.
Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, DK-1353 Copenhagen, Denmark.
Int J Mol Sci. 2021 Mar 10;22(6):2790. doi: 10.3390/ijms22062790.
Sudden cardiac death (SCD) is a diagnostic challenge in forensic medicine. In a relatively large proportion of the SCDs, the deaths remain unexplained after autopsy. This challenge is likely caused by unknown disease mechanisms. Changes in DNA methylation have been associated with several heart diseases, but the role of DNA methylation in SCD is unknown. In this study, we investigated DNA methylation in two SCD subtypes, sudden unexplained death (SUD) and sudden unexpected death in epilepsy (SUDEP). We assessed DNA methylation of more than 850,000 positions in cardiac tissue from nine SUD and 14 SUDEP cases using the Illumina Infinium MethylationEPIC BeadChip. In total, six differently methylated regions (DMRs) between the SUD and SUDEP cases were identified. The DMRs were located in proximity to or overlapping genes encoding proteins that are a part of the glutathione S-transferase (GST) superfamily. Whole genome sequencing (WGS) showed that the DNA methylation alterations were not caused by genetic changes, while whole transcriptome sequencing (WTS) showed that DNA methylation was associated with expression levels of the gene. In conclusion, our results indicate that cardiac DNA methylation is similar in SUD and SUDEP, but with regional differential methylation in proximity to GST genes.
心脏性猝死（SCD）是法医学中的一个诊断难题。在相当大比例的 SCD 中，尸检后仍无法解释死因。这一挑战可能是由未知的疾病机制引起的。DNA 甲基化的变化与多种心脏病有关，但 DNA 甲基化在 SCD 中的作用尚不清楚。在这项研究中，我们研究了两种 SCD 亚型（突然不明原因死亡[SUD]和癫痫性猝死[SUD]）中的 DNA 甲基化。我们使用 Illumina Infinium MethylationEPIC BeadChip 评估了来自 9 例 SUD 和 14 例 SUDEP 病例的心脏组织中超过 850,000 个位置的 DNA 甲基化。总共鉴定出 SUD 和 SUDEP 病例之间的六个不同甲基化区域（DMR）。DMR 位于谷胱甘肽 S-转移酶（GST）超家族编码蛋白的基因附近或重叠。全基因组测序（WGS）表明，DNA 甲基化的改变不是由遗传变化引起的，而全转录组测序（WTS）表明，DNA 甲基化与基因的表达水平有关。总之，我们的研究结果表明，SUD 和 SUDEP 患者的心脏 DNA 甲基化相似，但 GST 基因附近存在区域差异甲基化。
