Institute of Bioimaging and Complex Biological Systems (IBSBC), National Research Council (CNR), Section of Catanzaro, 88100 Catanzaro, Italy.
Institute for Biomedical Research and Innovation (IRIB), National Research Council (CNR) Cosenza, 88100 Catanzaro, Italy.
Int J Mol Sci. 2024 Aug 16;25(16):8921. doi: 10.3390/ijms25168921.
According to various research, the risk of multiple sclerosis (MS) is strongly influenced by genetic variations. Population, familial, and molecular studies provide strong empirical support for a polygenic pattern of inheritance, mainly due to relatively common allelic variants in the general population. The strongest MS susceptibility locus, which was unmistakably identified in tested populations, is the major histocompatibility complex on chromosome 6p21.3. However, the effect of a given predisposing variant remains modest, so there is the possibility that multiple gene-gene and/or gene-environment interactions could significantly increase the contribution of specific variants to the overall genetic risk. Furthermore, as is known, susceptibility genes can be subject to epigenetic modifications, which greatly increase the complexity of MS heritability. Investigating epigenetic and environmental factors can provide new opportunities for the molecular basis of the MS, which shows complicated pathogenesis. Although studies of epigenetic changes in MS only began in the last decade, a growing body of literature suggests that these may be involved in the development of MS. Here, we summarize recent studies regarding epigenetic changes related to MS initiation and progression. Furthermore, we discuss how current studies address important clinical questions and how future studies could be used in clinical practice.
根据各种研究,多发性硬化症 (MS) 的风险受遗传变异的强烈影响。人群、家族和分子研究为多基因遗传模式提供了强有力的经验支持,主要是由于常见的等位基因变异在普通人群中相对普遍。在经过测试的人群中明确识别出的最强 MS 易感性基因座是染色体 6p21.3 上的主要组织相容性复合体。然而,给定易感性变异的影响仍然较小,因此多种基因-基因和/或基因-环境相互作用有可能显著增加特定变异对整体遗传风险的贡献。此外,众所周知,易感基因可能会受到表观遗传修饰的影响,这大大增加了 MS 遗传性的复杂性。研究表观遗传和环境因素可以为 MS 的分子基础提供新的机会,因为 MS 的发病机制非常复杂。尽管 MS 中表观遗传变化的研究仅在上个十年才开始,但越来越多的文献表明这些变化可能与 MS 的发展有关。在这里,我们总结了最近关于与 MS 发病和进展相关的表观遗传变化的研究。此外,我们还讨论了当前研究如何解决重要的临床问题,以及未来的研究如何在临床实践中应用。