Pain in Motion (PiM) international research group, Department of Physiotherapy, Human Physiology and Anatomy, Faculty of Rehabilitation Sciences & Physiotherapy, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Jette, Brussels, Belgium.
Department of Public Health and Primary Care, Centre for Environment & Health, KU Leuven, Kapucijnenvoer 35, 3000, Leuven, Belgium.
J Transl Med. 2022 Oct 25;20(1):487. doi: 10.1186/s12967-022-03662-7.
Catechol-O-methyltransferase (COMT) has been shown to influence clinical pain, descending modulation, and exercise-induced symptom worsening. COMT regulates nociceptive processing and inflammation, key pathophysiological features of Chronic Fatigue Syndrome and Fibromyalgia (CFS/FM). We aimed to determine the interactions between genetic and epigenetic mechanisms regulating COMT and its influence on inflammatory markers and symptoms in patients with CFS/FM.
A case-control study with repeated-measures design was used to reduce the chance of false positive and increase the power of our findings. Fifty-four participants (28 patients with CFS/FM and 26 controls) were assessed twice within 4 days. The assessment included clinical questionnaires, neurophysiological assessment (pain thresholds, temporal summation, and conditioned pain modulation), and blood withdrawal in order to assess rs4818, rs4633, and rs4680 COMT polymorphisms and perform haplotype estimation, DNA methylation in the COMT gene (both MB-COMT and S-COMT promoters), and cytokine expression (TNF-α, IFN-γ, IL-6, and TGF-β).
COMT haplotypes were associated with DNA methylation in the S-COMT promoter, TGF-β expression, and symptoms. However, this was not specific for one condition. Significant between-group differences were found for increased DNA methylation in the MB-COMT promoter and decreased IFN-γ expression in patients.
Our results are consistent with basic and clinical research, providing interesting insights into genetic-epigenetic regulatory mechanisms. MB-COMT DNA methylation might be an independent factor contributing to the pathophysiology of CFS/FM. Further research on DNA methylation in complex conditions such as CFS/FM is warranted. We recommend future research to employ a repeated-measure design to control for biomarkers variability and within-subject changes.
儿茶酚氧位甲基转移酶（COMT）已被证明会影响临床疼痛、下行调制和运动引起的症状恶化。COMT 调节伤害感受处理和炎症，这是慢性疲劳综合征和纤维肌痛（CFS/FM）的关键病理生理特征。我们旨在确定调节 COMT 的遗传和表观遗传机制之间的相互作用及其对 CFS/FM 患者炎症标志物和症状的影响。
采用病例对照研究和重复测量设计，以减少假阳性的机会并提高我们发现的效力。54 名参与者（28 名 CFS/FM 患者和 26 名对照）在 4 天内进行了两次评估。评估包括临床问卷、神经生理学评估（疼痛阈值、时间总和和条件性疼痛调制）以及血液采集，以评估 rs4818、rs4633 和 rs4680 COMT 多态性并进行单倍型估计、COMT 基因中的 DNA 甲基化（MB-COMT 和 S-COMT 启动子）和细胞因子表达（TNF-α、IFN-γ、IL-6 和 TGF-β）。
COMT 单倍型与 S-COMT 启动子中的 DNA 甲基化、TGF-β 表达和症状相关。然而，这并不是特定于一种情况的。与对照组相比，患者的 MB-COMT 启动子中 DNA 甲基化增加和 IFN-γ 表达减少存在显著的组间差异。
我们的结果与基础和临床研究一致，为遗传-表观遗传调节机制提供了有趣的见解。MB-COMT DNA 甲基化可能是 CFS/FM 病理生理学的一个独立因素。需要对 CFS/FM 等复杂疾病中的 DNA 甲基化进行进一步研究。我们建议未来的研究采用重复测量设计来控制生物标志物的变异性和个体内变化。
Zotero 插件