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严重创伤性损伤与DNA甲基化的深刻变化有关。

Severe traumatic injury is associated with profound changes in DNA methylation.

作者信息

Eskesen Trine O, Almstrup Kristian, Elgaard Laurits, Arleth Tobias, Lassen Mathilde L, Creutzburg Andreas, Jensen Alice Herrlin, Breindahl Niklas, Dinesen Felicia, Vang Malene, Sørensen Erik, Paulsen Anders Wallin, Nielsen Tatiana, Rasmussen Lars S, Sillesen Martin, Steinmetz Jacob

机构信息

Department of Anesthesia, Section 6011, Center of Head and Orthopedics, Rigshospitalet, Copenhagen, Denmark.

Department of Growth and Reproduction, Rigshospitalet, Copenhagen, Denmark.

出版信息

NPJ Genom Med. 2024 Nov 1;9(1):53. doi: 10.1038/s41525-024-00438-4.

DOI:10.1038/s41525-024-00438-4
PMID:39487175
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11530621/
Abstract

Whether DNA methylation changes follow human physical trauma is uncertain. We aimed to investigate if severe trauma was associated with DNA methylation changes. In a prospective, observational, clinical study, we included severely injured adults and adults undergoing elective surgery (controls). Blood was obtained from trauma patients (n = 60) immediately- and 30-45 days post-trauma, and from surgical patients (n = 57) pre-, post-, and 30-45 days post-surgery. Epigenome-wide DNA methylation profiling was performed and analyzed for significant differentially methylated CpGs and -regions (DMRs) within and between groups. Within the trauma group we identified 10,126 significant differentially methylated CpGs and 1169 DMRs. No significant differential methylation was found in the surgical group. In the trauma group, differentially methylated sites were enriched in genes and pathways involved in blood coagulation and inflammatory response. Severe trauma was associated with profound alterations in the DNA methylome of circulating leucocytes, and differential methylation was located in trauma-relevant genes.

摘要

DNA甲基化变化是否伴随人类身体创伤尚不确定。我们旨在研究严重创伤是否与DNA甲基化变化相关。在一项前瞻性、观察性临床研究中,我们纳入了重伤成年人和接受择期手术的成年人(对照组)。在创伤后即刻以及创伤后30 - 45天采集创伤患者(n = 60)的血液,在手术前、手术后以及手术后30 - 45天采集手术患者(n = 57)的血液。进行全基因组DNA甲基化分析,并分析组内和组间显著差异甲基化的CpG和区域(DMR)。在创伤组中,我们鉴定出10126个显著差异甲基化的CpG和1169个DMR。手术组未发现显著的差异甲基化。在创伤组中,差异甲基化位点在参与凝血和炎症反应的基因及通路中富集。严重创伤与循环白细胞DNA甲基化组的深刻改变相关,且差异甲基化位于与创伤相关的基因中。

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本文引用的文献

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Association of Trauma With Long-Term Risk of Death and Immune-Mediated or Cancer Disease in Same-Sex Twins.创伤与同卵双胞胎长期死亡风险及免疫介导或癌症疾病的关联。
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Epigenome-wide meta-analysis of PTSD across 10 military and civilian cohorts identifies methylation changes in AHRR.创伤后应激障碍的全基因组甲基化荟萃分析跨越 10 个军事和民用队列,确定了 AHRR 中的甲基化变化。
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DNA hydroxymethylation mediated traumatic spinal injury by influencing cell death-related gene expression.DNA 羟甲基化通过影响细胞死亡相关基因表达介导外伤性脊髓损伤。
J Cell Biochem. 2018 Nov;119(11):9295-9302. doi: 10.1002/jcb.27200. Epub 2018 Aug 3.
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Epigenetic Mechanisms of Traumatic Brain Injuries.创伤性脑损伤的表观遗传机制。
Prog Mol Biol Transl Sci. 2018;157:263-298. doi: 10.1016/bs.pmbts.2017.12.013. Epub 2018 Apr 11.
10
Childhood Trauma, DNA Methylation of Stress-Related Genes, and Depression: Findings From Two Monozygotic Twin Studies.童年创伤、应激相关基因的 DNA 甲基化与抑郁:两项同卵双生子研究的结果。
Psychosom Med. 2018 Sep;80(7):599-608. doi: 10.1097/PSY.0000000000000604.