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DNA methylation differences in genes associated with human personal disorders and deviant behavior

机译:与人类个人疾病和越轨行为相关的基因的 DNA 甲基化差异

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摘要

Epigenetic regulation of gene expression is involved in the progression of mental disorders, including deviant behavior, brain developmental, and personality disorders. The large number of genes has been studied for their activity association with stress and depression; however, the obtained results for the majority of these genes are contradictory. The aim of our study was to investigate the possible contribution of methylation level changes to the development of personality disorders and deviant behavior. A systematic study of CpG Islands in 21 target regions, including the promoter and intron regions of the 12 genes was performed in DNA samples extracted from peripheral blood cells, to obtain an overview of their methylation status. High-throughput sequencing of converted DNA samples was performed and calling of the methylation sites on the “original top strand” in CpG islands was carried out in the Bismark pipeline. The initial methylation profile of 77 patients and 48 controls samples revealed a significant difference in 7 CpG sites in 6 genes. The most significant hypermethylation was found for the target sites of the HTR2A (p-value = 1.2 × 10−13) and OXTR (p-value = 2.3 × 10−7) genes. These data support the previous reports that alterations in DNA methylation may play an important role in the dysregulation of gene expression associated with personality disorders and deviant behavior, and confirm their potential use as biomarkers to improve thediagnosis, prognosis, and assessment of response to treatment.
机译:基因表达的表观遗传调控与精神障碍的进展有关,包括越轨行为、大脑发育和人格障碍。已经研究了大量基因的活动与压力和抑郁的关联;然而,这些基因中的大多数获得的结果是矛盾的。我们研究的目的是调查甲基化水平变化对人格障碍和越轨行为发展的可能贡献。对 21 个靶区的 CpG 岛进行了系统研究,包括 12 个基因的启动子和内含子区,从外周血细胞中提取的 DNA 样品中,以获得其甲基化状态的概述。对转化的 DNA 样品进行高通量测序,并在 Bismark 管道中对 CpG 岛中“原始顶链”上的甲基化位点进行检出。77 例患者和 48 例对照样品的初始甲基化谱显示 6 个基因的 7 个 CpG 位点存在显著差异。在 HTR2A (p 值 = 1.2 × 10-13) 和 OXTR (p 值 = 2.3 × 10-7) 基因的靶位点发现最显著的高甲基化。这些数据支持先前的报道,即 DNA 甲基化的改变可能在与人格障碍和越轨行为相关的基因表达失调中发挥重要作用,并证实了它们作为生物标志物的潜在用途,以改善诊断、预后和对治疗反应的评估。

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