Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
Physiol Genomics. 2017 Sep 1;49(9):447-461. doi: 10.1152/physiolgenomics.00060.2017. Epub 2017 Jul 28.
Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of the central nervous system. MS likely results from a complex interplay between predisposing causal gene variants (the strongest influence coming from HLA class II locus) and environmental risk factors such as smoking, infectious mononucleosis, and lack of sun exposure/vitamin D. However, little is known about the mechanisms underlying MS development and progression. Moreover, the clinical heterogeneity and variable response to treatment represent additional challenges to a comprehensive understanding and efficient treatment of disease. Epigenetic processes, such as DNA methylation and histone posttranslational modifications, integrate influences from the genes and the environment to regulate gene expression accordingly. Studying epigenetic modifications, which are stable and reversible, may provide an alternative approach to better understand and manage disease. We here aim to review findings from epigenetic studies in MS and further discuss the challenges and clinical opportunities arising from epigenetic research, many of which apply to other diseases with similar complex etiology. A growing body of evidence supports a role of epigenetic processes in the mechanisms underlying immune pathogenesis and nervous system dysfunction in MS. However, disparities between studies shed light on the need to consider possible confounders and methodological limitations for a better interpretation of the data. Nevertheless, translational use of epigenetics might offer new opportunities in epigenetic-based diagnostics and therapeutic tools for a personalized care of MS patients.
多发性硬化症（MS）是一种中枢神经系统的慢性炎症性脱髓鞘疾病。MS 可能是由易感性因果基因变异（最强的影响来自 HLA Ⅱ类基因座）与环境风险因素（如吸烟、传染性单核细胞增多症和缺乏阳光暴露/维生素 D）之间的复杂相互作用所致。然而，对于 MS 发病和进展的机制，我们知之甚少。此外，临床异质性和对治疗的不同反应，进一步增加了对疾病的全面理解和有效治疗的挑战。表观遗传过程，如 DNA 甲基化和组蛋白翻译后修饰，整合了基因和环境的影响，以相应地调节基因表达。研究表观遗传修饰（其稳定且可逆）可能提供一种替代方法，以更好地理解和管理疾病。我们旨在回顾 MS 中表观遗传学研究的结果，并进一步讨论表观遗传学研究带来的挑战和临床机遇，其中许多适用于具有类似复杂病因的其他疾病。越来越多的证据表明，表观遗传过程在 MS 免疫发病机制和神经系统功能障碍的机制中发挥作用。然而，研究之间的差异表明，需要考虑可能的混杂因素和方法学限制，以更好地解释数据。尽管如此，表观遗传学的转化应用可能为 MS 患者的个性化治疗提供基于表观遗传学的诊断和治疗工具的新机遇。
