The evidence suggesting a role of epigenetics in the definition of complex trait diseases is rapidly increasing. The gender prevalence of multiple sclerosis, the low level concordance in homozygous twins and the linkage to several genetic loci, suggest an epigenetic component to the definition of this demyelinating disorder. While the immune etio-pathogenetic mechanism of disease progression has been well characterized, still relatively little is known about the initial events contributing to onset and progression of the demyelinating lesion. This article addresses the challenging question of whether loss of the mechanisms of epigenetic regulation of gene expression in the myelinating cells may contribute to the pathogenesis of multiple sclerosis, by affecting the repair process and by modulating the levels of enzymes involved in neo-epitope formation. The role of altered post-translational modifications of nucleosomal histones and DNA methylation in white matter oligodendroglial cells are presented in terms of pathogenetic concepts and the relevance to therapeutic intervention is then discussed.

中文翻译：

---

评估多发性硬化症患者大脑中的表观遗传学标志：对当前有关疾病发病机制的辩论的贡献。

证据表明表观遗传学在复杂性状疾病定义中的作用正在迅速增加。多发性硬化症的性别患病率，纯合双胞胎中的低水平一致性以及与几个遗传基因座的联系，暗示了该脱髓鞘疾病的定义的表观遗传成分。尽管已经很好地表征了疾病进展的免疫病因-发病机理，但对于引起脱髓鞘病变的发作和进展的初始事件知之甚少。本文解决了一个具有挑战性的问题，即髓鞘细胞中基因表达的表观遗传调控机制的丧失是否可能导致多发性硬化症的发病机理，通过影响修复过程和调节新表位形成所涉及的酶水平。根据病原学概念，介绍了核小体组蛋白的翻译后修饰修饰和DNA甲基化在白质少突胶质细胞中的作用，然后讨论了与治疗干预的相关性。