Changes in the Expression of DNA Methylation Related Genes in Leukocytes of Persons with Alcohol and Drug Dependence

Abstract

Abstract Background and objectives. Though numerous studies have shown that the dysregulation of the epigenetic control is involved in disease manifestation, limited data is available on the transcriptional activity of DNA methylation related genes in alcohol and drug addiction. With regard to this, in this study we analyzed the expression levels of genes involved in DNA methylation, including DNMT1, DNMT3a, MeCP2, MBD1, MBD2, MBD3 and MBD4, in blood samples of alcohol and drug dependent persons in comparison to healthy abstainers. Methods. The study included 51 participants: 16 persons with alcohol dependence, 17 persons with drug dependence and 18 clinically healthy controls. To detect the relative mRNA expression levels of the studied genes, Quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis was applied. Results. Of the seven studied genes, four showed altered expression. MeCP2 and MBD1 were downregulated in the alcohol dependent group (FC = 0.805, p = 0.015 and FC = 0.846, p = 0.034, respectively), while DNMT1 and MBD4 were upregulated in the group with drug dependence (FC = 1.262, p = 0.001 and FC = 1.249, p = 0.005, respectively). No statistically significant changes in the relative mRNA expression were found for DNMT3a, MBD2 and MBD3 genes. Conclusions. Our results are indicative for a role of DNA methylation related genes in alcohol and drug addiction mediated through changes in their transcriptional activity. Studies in this direction will enable better understanding of the underlying mechanisms of addictions supporting the development of more effective therapeutic strategies.