Abstract
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 (DAT1) promoter CpG sites and cannabis dependency. In the cases of some DNA sequences, including the DAT1 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 DAT1 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, DAT1 gene promoter methylation studies may provide important insight into the mechanism of cannabis dependency.
Highlights
Epigenetics refers to the processes that modify the regulation of genes without disrupting the DNA sequence
Due to the crucial role the dopaminergic system plays in all substance use disorders, we looked to analyze the methylation status of 33 CpG sites located in the dopamine transporter gene promoter region in a group of cannabis dependent subjects
We evaluated the effect of cannabis dependency on the DAT1 promoter methylation status in patients’ peripheral blood leucocytes in a side-by-side comparison with healthy individuals
Summary
Epigenetics refers to the processes that modify the regulation of genes without disrupting the DNA sequence. These processes may result in distinguishing a phenotype [1,2,3,4,5]. Brain Sci. 2020, 10, 400 be turned on or off, which is associated with exposure to certain agents, such as psychoactive substances. Epigenetic alterations, including methylation status, might reflect environmental conditions and a person’s lifestyle. Epigenetics may become a vital aspect of clinical diagnostics, as it encompasses the regulation of gene expression mediated by DNA methylation, nucleosome structure and positioning, posttranslational modifications of nucleosome histones, histone replacement, and RNA interference [10]. We understand that epigenetic alterations function to repress or activate genes, but since they are not fully understood, they may have other functions
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