Graves Letitia Y, Alcorn Melissa R, Chan E Ricky, Schwartz Katelyn, Henzel M Kristi, Galea Marinella, Toth Anna M, Olney Christine M, Bogie Kath M
VA Northeast Ohio Healthcare System, Cleveland, OH 44106, USA.
School of Nursing, University Texas Medical Branch at Galveston, Galveston, TX 77555, USA.
Epigenomes. 2025 Jul 23;9(3):26. doi: 10.3390/epigenomes9030026.
BACKGROUND/OBJECTIVES: This study investigated variations in DNA methylation patterns associated with chronic pain and propensity for recurrent pressure injuries (PrI) in persons with spinal cord injury (SCI).
Whole blood was collected from 81 individuals with SCI. DNA methylation was quantified using Illumina genome-wide arrays (EPIC and EPICv2). Comprehensive clinical profiles collected included secondary health complications, in particular current PrI and chronic pain. Relationships between recurrent PrI and chronic pain and whether the co-occurrence of both traits was mediated by changes in DNA methylation were investigated using R packages limma, DMRcate and mCSEA.
Three differentially methylated positions (DMPs) (cg09867095, cg26559694, cg24890286) and one region in the micro-imprinted locus for are associated with chronic pain in persons with SCI. The study cohort was stratified by PrI status to identify any sites associated with chronic pain and while the same three sites and region were replicated in the group with no recurrent PrI, two novel, hypermethylated (cg21756558, cg26217441) sites and one region in the protein-coding gene were identified in the group with recurrent PrI. Gene enrichment and genes associated with specific promoters using MetaScape identified several shared disorders and ontology terms between independent phenotypes of pain and recurrent PrI and interactive sub-groups.
DMR analysis using mCSEA identified several shared genes, promoter-associated regions and CGI associated with overall pain and PrI history, as well as sub-groups based on recurrent PrI history. These findings suggest that a much larger gene regulatory network is associated with each phenotype. These findings require further validation.
背景/目的：本研究调查了脊髓损伤（SCI）患者中与慢性疼痛及复发性压疮（PrI）倾向相关的DNA甲基化模式变化。
采集了81名SCI患者的全血。使用Illumina全基因组芯片（EPIC和EPICv2）对DNA甲基化进行定量分析。收集的综合临床资料包括继发性健康并发症，尤其是当前的PrI和慢性疼痛。使用R包limma、DMRcate和mCSEA研究复发性PrI与慢性疼痛之间的关系，以及这两种特征的同时出现是否由DNA甲基化变化介导。
三个差异甲基化位点（DMPs）（cg09867095、cg26559694、cg24890286）以及 微印记基因座中的一个区域与SCI患者的慢性疼痛相关。根据PrI状态对研究队列进行分层，以确定与慢性疼痛相关的任何位点。虽然在无复发性PrI的组中重复出现了相同的三个位点和区域，但在有复发性PrI的组中鉴定出了两个新的高甲基化位点（cg21756558、cg26217441）以及蛋白质编码基因 中的一个区域。使用MetaScape进行基因富集和与特定启动子相关的基因分析，确定了疼痛和复发性PrI独立表型以及相互作用亚组之间的几个共同疾病和本体术语。
使用mCSEA进行的差异甲基化区域（DMR）分析确定了几个与总体疼痛和PrI病史相关的共同基因、启动子相关区域和CpG岛，以及基于复发性PrI病史的亚组。这些发现表明，每个表型都与一个更大的基因调控网络相关。这些发现需要进一步验证。
