Abstract

This study aims to investigate the association between cannabinoid use disorder (CUD) or synthetic cannabinoid use disorder (SCUD) and methylation status of MB-COMT (membrane-bound catechol-O-methyltransferase) promotor or DRD2 gene considering gene variants and clinical parameters. Based on the DSM-5 criteria, 218 CUD/SCUD patients’ diagnoses were confirmed with a positive urine test, and a control group consisting of 102 participants without substance use disorders was included. Methylation-specific PCR was used to identify the methylation of the MB-COMT promotor and DRD2 gene. DRD2-141C Ins/Del and COMT Val158Met gene variants were evaluated by using PCR-RFLP. When the DRD2 and MB-COMT promoter methylation of CUD/SCUD patients were compared with the control group, there was a significant difference between the MB-COMT promoter methylation status of the two groups. When comparing DRD2 gene methylation due to clinical parameters and DRD2 genotype distribution in patients, the methylation status was significantly different between the groups due to the family history. Again, comparing the MB-COMT promotor methylation due to the COMT Val158Met genotype distribution and clinical parameters in patients, the MB-COMT promoter methylation status was significantly different between the groups due to the presence of alcohol usage. In summary, whereas the MB-COMT promoter methylation may be associated with the CUD/SCUD, the methylation of the DRD2 gene was not related to CUD/SCUD.

摘要

本研究旨在考虑基因变异和临床参数，研究大麻素使用障碍 (CUD) 或合成大麻素使用障碍 (SCUD) 与 MB-COMT（膜结合儿茶酚-O-甲基转移酶）启动子或 DRD2 基因甲基化状态之间的关联。根据 DSM-5 标准，218 名 CUD/SCUD 患者的诊断通过尿检阳性得到确认，并包括一个由 102 名没有物质使用障碍的参与者组成的对照组。甲基化特异性 PCR 用于鉴定 MB-COMT 启动子和 DRD2 基因的甲基化。通过使用 PCR-RFLP 评估 DRD2-141C Ins/Del 和 COMT Val158Met 基因变异。与对照组比较CUD/SCUD患者的DRD2和MB-COMT启动子甲基化时，两组的MB-COMT启动子甲基化状态存在显着差异。当比较由于临床参数引起的 DRD2 基因甲基化和患者的 DRD2 基因型分布时，由于家族史，各组之间的甲基化状态存在显着差异。同样，比较由于 COMT Val158Met 基因型分布和患者临床参数导致的 MB-COMT 启动子甲基化，由于饮酒的存在，各组之间的 MB-COMT 启动子甲基化状态显着不同。总之，虽然 MB-COMT 启动子甲基化可能与 CUD/SCUD 相关，但 DRD2 基因的甲基化与 CUD/SCUD 无关。由于家族史，各组之间的甲基化状态存在显着差异。同样，比较由于 COMT Val158Met 基因型分布和患者临床参数导致的 MB-COMT 启动子甲基化，由于饮酒的存在，各组之间的 MB-COMT 启动子甲基化状态显着不同。总之，虽然 MB-COMT 启动子甲基化可能与 CUD/SCUD 相关，但 DRD2 基因的甲基化与 CUD/SCUD 无关。由于家族史，各组之间的甲基化状态存在显着差异。同样，比较由于 COMT Val158Met 基因型分布和患者临床参数导致的 MB-COMT 启动子甲基化，由于饮酒的存在，各组之间的 MB-COMT 启动子甲基化状态显着不同。总之，虽然 MB-COMT 启动子甲基化可能与 CUD/SCUD 相关，但 DRD2 基因的甲基化与 CUD/SCUD 无关。