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检测大麻或合成大麻素使用障碍患者中 MB-COMT 启动子和 DRD2 基因的甲基化改变与基因变异和临床参数的关系。

Detection of altered methylation of MB-COMT promotor and DRD2 gene in cannabinoid or synthetic cannabinoid use disorder regarding gene variants and clinical parameters.

机构信息

Department of Medical Biology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.

Department of Psychiatry, Basaksehir Cam and Sakura City Hospital, Istanbul, Turkey.

出版信息

J Addict Dis. 2021 Oct-Dec;39(4):526-536. doi: 10.1080/10550887.2021.1906618. Epub 2021 Mar 29.

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

本研究旨在探讨大麻素使用障碍(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,同时考虑基因变异和临床参数。根据 DSM-5 标准,通过阳性尿液检测,对 218 名 CUD/SCUD 患者的诊断进行了确认,并纳入了 102 名无物质使用障碍的对照组。使用甲基化特异性 PCR 来鉴定 MB-COMT 启动子和 DRD2 基因的甲基化。通过 PCR-RFLP 评估 DRD2-141C Ins/Del 和 COMT Val158Met 基因变异。当比较 CUD/SCUD 患者的 DRD2 和 MB-COMT 启动子甲基化与对照组时,两组之间的 MB-COMT 启动子甲基化状态存在显著差异。当比较患者的临床参数和 DRD2 基因型分布导致的 DRD2 基因甲基化时,由于家族史,两组之间的甲基化状态存在显著差异。此外,比较患者的 COMT Val158Met 基因型分布和临床参数导致的 MB-COMT 启动子甲基化时,由于存在酒精使用,两组之间的 MB-COMT 启动子甲基化状态存在显著差异。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。

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