Investigation of epigenetic differences in patients with substance use disorders and comparison with clinical parameters

Substance use disorder (SUD) is one of the most important public health problems facing all countries, including our country. The formation and course of SUD depends on different molecular and cellular mechanisms and environmental factors. Genetic and epigenetic studies have shown that some genes are associated with SUD. Genes that play a role especially in dopaminergic pathways have been the focus of the study of SUD. In our study, it was aimed to compare the demographic and clinical parameters with the Val158Met functional variant of the COMT gene, which is effective in the dopaminergic system, with the membrane-bound (MB-COMT) form, the DRD2 gene, which is the dopamine receptor gene, the -141C Ins/Del functional variant and the DRD2 methylation analysis. As control group, 102 individuals and 218 individuals diagnosed with SUD were included in the study. Restriction fragment length polymorphism (PCR-RFLP) method was used for analysis of gene variants and Methylation-specific PCR (MSP) method was used for methylation analysis. The results were statistically analyzed using Pearson chi-square test and Fisher Exact test, and p <0.05 was considered statistically significant. When comparing the SUD group and the control group, no statistically significant difference was observed in the genotype and allele frequencies of the COMT Val158Met and DRD2 -141C variants (p> 0.05). However, Val158Met variant Val/Met genotype was found statistically significantly higher in individuals diagnosed with psychotic symptoms (p <0.001). Multiple substance use is also significantly higher in Val allele carriers (p <0.05). -141C variant Ins allele was significantly higher in individuals with a family psychiatric disorder (p <0.05). According to MB-COMT methylation analysis, while MKB individuals were found to have lower methylation frequency compared to the control group (p <0.001), there was no statistically significant difference compared to DRD2 methylation analysis (p> 0.05). In conclusion, it was observed in this study that COMT and DRD2 functional gene variants have significant relationships with various clinical parameters and that hypomethylation of MB-COMT may be an important factor for SUD.