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Updated: Jun 27, 2025

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双极性疾病中的反应:全表观基因组的DNA甲基化特征和表观基因衰老

Marina Zafrilla-López¹, Miriam Acosta-Díez¹, Marina Mitjans²

¹Department of Evolutionary Biology, Ecology and Environmental Sciences, Faculty of Biology, University of Barcelona, Barcelona, Spain.

European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology

|April 26, 2024

概括

特定的DNA甲基化模式可以预测双相情感障碍 (BD) 患者的反应. 虽然表观遗传年龄没有差异,但确定了与反应和GSK3β通路相关的关键基因,这表明表观遗传在治疗疗效方面发挥了作用.

科学领域:

神经科学是一个神经科学.
遗传学遗传学是一个
药理学药理学是指药理学的学科.

背景情况:

(Li) 是双相情感障碍 (BD) 的一线治疗方法,但只有30%的患者表现出极好的反应.
表观遗传机制,特别是DNA甲基化,涉及到BD和Li治疗,与表观遗传年龄 (EpiAge) 有潜在的联系.
之前的研究表明,治疗可以逆转BD患者的加速EpiAge.

研究的目的:

为了在BD患者中比较出色的Li响应者 (Ex-Rp) 和不响应者 (N-Rp) 之间的DNA甲基化概况.
估计和比较Ex-Rp和N-Rp之间的EpiAge,以确定差异性的年龄加速.
根据甲基化模式识别与Li反应相关的特定基因和途径.

主要方法:

对来自BD患者的外周血液样本进行了DNA甲基化分析,分类为Ex-Rp (n=26) 和N-Rp (n=37).
通过使用FDR调整的p值<0.05.5来确定差异甲基化位置 (DMP) 和区域 (DMR).
使用已建立的表观遗传钟估计了表观遗传年龄 (EpiAge);进行了基因丰富和网络分析.

主要成果:

在Ex-Rp和N-Rp之间确定了130个DMP和16个DMR,映射到122个基因.
之前与Li反应相关的9个基因 (例如HOXB6,ANK3) 是其中之一.
与GSK3β通路相关的基因具有很高的代表性,通路分析表明对突触功能和细胞循环调节的丰富. 两组之间没有发现年龄加速的显著差异.

结论:

特定的DNA甲基化模式可以在BD中区分Li响应者和非响应者.
GSK3β途径在反应中具有强烈的影响,加强了它在治疗疗效方面的作用.
除了总体表观遗传年龄之外,表观遗传机制可能在确定双相情感障碍患者对治疗的个体反应方面发挥着关键作用.

关键词:

双极性障碍是一种双极性障碍.通过DNA甲基化.基因表观衰老基因表观衰老基因表观衰老表观遗传学在表观遗传学中,表观遗传学是指表观遗传学.对的反应反应

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