Section on Clinical Genomics and Experimental Therapeutics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 10 Center Drive (10CRC), Bethesda, MD, USA.
Department of Psychiatry and Psychotherapy, Charité-Universitätsmedizin Berlin, Charitéplatz 1, Berlin, Germany.
Alcohol Alcohol. 2019 May 1;54(3):209-215. doi: 10.1093/alcalc/agz032.
Differences in DNA methylation of the serotonin transporter gene (SLC6A4) have been shown to alter SLC6A4 expression and predict brain functions in healthy individuals. This study investigated the association between SLC6A4 promoter methylation and threat-related amygdala activation in individuals with alcohol dependence (AD).
Methylation of the SLC6A4 promoter region was assessed using peripheral blood DNA from 45 individuals with AD and 45 healthy controls (HCs). All participants completed an emotional face matching task in a 3-T magnetic resonance imaging (MRI) scanner.
Results did not reveal any association between SLC6A4 promoter methylation variation and threat-related amygdala activation in HCs or individuals with AD. Furthermore, methylation in the promoter region of SLC6A4 did not significantly differ between the groups.
Our results do not replicate a previous finding that increased methylation in the promoter region of SLC6A4 is associated with threat-related amygdala activation in healthy individuals and further show that there is no such association in individuals with AD. Given that the number of imaging epigenetics studies on SLC6A4 is very limited to date, these inconsistent results indicate that future research is needed to clarify its association with amygdala reactivity in both healthy and clinical populations.
已有研究表明,5-羟色胺转运体基因(SLC6A4)的 DNA 甲基化差异会改变 SLC6A4 的表达,并预测健康个体的大脑功能。本研究旨在探讨酒精依赖(AD)个体中 SLC6A4 启动子甲基化与威胁相关杏仁核激活之间的关系。
使用 45 名 AD 患者和 45 名健康对照者(HCs)的外周血 DNA 评估 SLC6A4 启动子区域的甲基化。所有参与者在 3T 磁共振成像(MRI)扫描仪中完成了情绪面孔匹配任务。
结果显示,在 HCs 或 AD 患者中,SLC6A4 启动子甲基化变异与威胁相关杏仁核激活之间均不存在关联。此外,SLC6A4 启动子区域的甲基化在两组之间也没有显著差异。
本研究结果未能复制先前的发现,即 SLC6A4 启动子区域的甲基化增加与健康个体中威胁相关杏仁核激活有关,进一步表明 AD 患者中不存在这种关联。鉴于目前关于 SLC6A4 的影像学表观遗传学研究数量非常有限,这些不一致的结果表明,需要进一步的研究来明确其与健康人群和临床人群杏仁核反应性的关系。