Grzywacz Anna, Barczak Wojciech, Chmielowiec Jolanta, Chmielowiec Krzysztof, Suchanecka Aleksandra, Trybek Grzegorz, Masiak Jolanta, Jagielski Paweł, Grocholewicz Katarzyna, Rubiś Blazej
Independent Laboratory of Health Promotion, the Pomeranian Medical University in Szczecin, 11 Chlapowskiego St., 70-204 Szczecin, Poland.
Department of Head and Neck Surgery, Poznan University of Medical Sciences, Fredry 10, 61-701 Poznan, Poland.
Brain Sci. 2020 Jun 23;10(6):400. doi: 10.3390/brainsci10060400.
The susceptibility to cannabis dependency results from the influence of numerous factors such as social, genetic, as well as epigenetic factors. Many studies have attempted to discover a molecular basis for this disease. However, our study aimed at evaluating the connection between altered methylation of the dopamine transporter gene () promoter CpG sites and cannabis dependency. In the cases of some DNA sequences, including the gene region, their methylation status in blood cells may reflect a systemic modulation in the whole organism. Consequently, we isolated the DNA from the peripheral blood cells from a group of 201 cannabis-dependent patients and 285 controls who were healthy volunteers and who were matched for age and sex. The DNA was subjected to bisulfite conversion and sequencing. Our analysis revealed no statistical differences in the general methylation status of the gene promoter CpG island between the patients and controls. Yet, the analysis of individual CpG sites where methylation occurred indicated significant differences. These sites are known to be bound by transcription factors (e.g., SP1, p53, PAX5, or GR), which, apart from other functions, were shown to play a role in the development of the nervous system. Therefore, gene promoter methylation studies may provide important insight into the mechanism of cannabis dependency.
大麻依赖易感性源于多种因素的影响，如社会、遗传以及表观遗传因素。许多研究试图探寻这种疾病的分子基础。然而，我们的研究旨在评估多巴胺转运体基因（）启动子CpG位点甲基化改变与大麻依赖之间的关联。在某些DNA序列的情况下，包括基因区域，它们在血细胞中的甲基化状态可能反映整个生物体的系统性调节。因此，我们从一组201名大麻依赖患者和285名对照（健康志愿者，年龄和性别匹配）的外周血细胞中分离出DNA。对DNA进行亚硫酸氢盐转化和测序。我们的分析显示，患者和对照之间基因启动子CpG岛的总体甲基化状态没有统计学差异。然而，对发生甲基化的单个CpG位点的分析表明存在显著差异。已知这些位点会被转录因子（如SP1、p53、PAX5或GR）结合，除其他功能外，这些转录因子在神经系统发育中发挥作用。因此，基因启动子甲基化研究可能为大麻依赖的机制提供重要见解。
