Laboratory of Cyto-Molecular Genetics, Department of Anatomy, AIIMS, New Delhi 110029, India.
Department of Nuclear Medicine, AIIMS, New Delhi 110029, India.
Psychiatry Res Neuroimaging. 2020 Nov 30;305:111187. doi: 10.1016/j.pscychresns.2020.111187. Epub 2020 Sep 10.
Drug dependence associated with increased dopamine neurotransmission and neuroplastic changes is influenced by Dopamine transporters (DAT) which are modulated by genetic and epigenetic factors. This study assesses DAT availability in relation to the 40bp DAT1 VNTR (genetic) and DAT1 promoter methylation (epigenetic) changes in patients with alcohol dependence (AD) and opioid dependence (OD). A total of 60 subjects (n=20 each of AD, OD and controls) were recruited. SPECT/CT imaging using Tc-TRODAT-1 was performed for measuring striatal DAT availability and DNA screened to check DAT1promoter methylation and 40bp VNTR polymorphism. SPECT/CT imaging revealed significant decrease in DAT availability in the striatum and putamen and significant increase in DAT1 promoter methylation in AD compared to control and OD. The 40bp VNTR distribution was similar in all three groups with 10repeat and 9repeat alleles being the most common. The AD individuals with DAT1promoter methylation showed significantly lower TRODAT-1 uptake compared to the ones with no methylation. AD individuals homozygous for the 10repeat VNTR also showed reduced DAT availability. This is the first imaging study using Tc-TRODAT-1 from India documenting significantly reduced striatal DAT availability, increased DAT methylation and frequency of 10repeat individuals associated with decreased DAT availability in AD.
与多巴胺神经传递和神经可塑性变化相关的药物依赖受多巴胺转运体（DAT）的影响，DAT 受遗传和表观遗传因素的调节。本研究评估了酒精依赖（AD）和阿片类药物依赖（OD）患者 DAT 可用性与 DAT1 40bp VNTR（遗传）和 DAT1 启动子甲基化（表观遗传）变化的关系。共招募了 60 名受试者（AD、OD 和对照组各 20 名）。使用 Tc-TRODAT-1 进行 SPECT/CT 成像，以测量纹状体 DAT 的可用性，并筛查 DNA 以检查 DAT1 启动子甲基化和 40bp VNTR 多态性。SPECT/CT 成像显示 AD 患者与对照组和 OD 相比，纹状体和壳核中的 DAT 可用性明显降低，DAT1 启动子甲基化明显增加。三组中 40bp VNTR 分布相似，10 重复和 9 重复等位基因最常见。DAT1 启动子甲基化的 AD 个体与无甲基化的个体相比，TRODAT-1 摄取明显降低。10 重复 VNTR 纯合的 AD 个体也表现出 DAT 可用性降低。这是印度首次使用 Tc-TRODAT-1 进行的成像研究，记录了 AD 患者纹状体 DAT 可用性显著降低、DAT 甲基化增加以及与 DAT 可用性降低相关的 10 重复个体的频率增加。
