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表观遗传调控 DAT 基因启动子调节规范人群中外显和内隐行为的风险:一项探索性研究。

Epigenetic regulation of DAT gene promoter modulates the risk of externalizing and internalizing behaviors on a normative population: An explorative study.

机构信息

Center for Behavioral Science and Mental Health - Istituto Superiore di Sanità, Rome, Italy.

Faculty of Psychology - Uninettuno University, Rome, Italy.

出版信息

Behav Brain Res. 2021 May 21;406:113246. doi: 10.1016/j.bbr.2021.113246. Epub 2021 Mar 18.

DOI:10.1016/j.bbr.2021.113246
PMID:33745985
Abstract

Accumulating research addressed epigenetic modifications and their role on behavioral phenotypes. We recently proposed to study methylation dynamics of two CpG motifs within the 5'-UTR of dopamine transporter (DAT) gene. Starting from a normative population sample of young adults, we selected three sub-groups based on their prevalent symptoms: subjects were assigned to Internalizing, Externalizing and Low-risk sub-groups according to elevated scores in specific phenotypic scales. Using a new approach, we calculated three independent matrixes of cross-correlation between CpG methylation levels, one within each phenotypic sub-group, to determine in which dynamics did the sub-groups differ. We found specific cross-correlation patterns in Externalizing (CpG1, 2 and 3, opposite to the methylation at CpG6) and Internalizing individuals (CpG1 methylation opposite to CpG2, 3 and 6), while Low-risk individuals could follow both trends. The aim of our study was to look for a specific DAT methylation pattern, providing a biomarker that allows early identification of the risk for psycho-pathological deviance.

摘要

越来越多的研究关注表观遗传修饰及其在行为表型中的作用。我们最近提出研究多巴胺转运体(DAT)基因 5'UTR 中两个 CpG 基序的甲基化动态。从年轻成年人的正常人群样本开始,我们根据其常见症状选择了三个亚组:根据特定表型量表中升高的分数,将受试者分配到内化、外化和低风险亚组。我们使用一种新方法,在每个表型亚组内计算了三个独立的 CpG 甲基化水平之间的互相关矩阵,以确定亚组在哪些动态中存在差异。我们在外化(CpG1、2 和 3,与 CpG6 的甲基化相反)和内化个体(CpG1 甲基化与 CpG2、3 和 6 相反)中发现了特定的互相关模式,而低风险个体可以遵循这两种趋势。我们研究的目的是寻找 DAT 甲基化的特定模式,提供一种生物标志物,能够早期识别心理病理偏差的风险。

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