CHN2 Promoter Methylation Change May Be Associated With Methamphetamine Dependence

Shanghai Arch Psychiatry. 2017 Dec 25;29(6):357-364. doi: 10.11919/j.issn.1002-0829.217100.

Abstract

Background: Methamphetamine (MA) abuse is becoming increasingly serious in China. The mechanism of MA dependence remains unclear. CHN2 gene encodes chimeric protein-2 that regulate axonal pruning via the Rac-GTPase system and play a pivotal role in the formation of nervous circuits. Genetic studies suggest that the polymorphism of the CHN2 gene was related to substance dependence.

Aims: The aim of this study was to investigate the association between the methylation of CHN2 gene promoter with MA dependence.

Methods: According to SCID-I (Structured Clinical Interview for DSM-IV Axis I Disorders, SCID-I) used for investigating MA dependence, 224 male MA addicts were recruited into the case group. In addition, 109 healthy men were recruited into the control group. Blood samples were collected with the purpose of detecting the methylation levels of CHN2 gene promoter by methylight qPCR. The association between the methylation of CHN2 gene promoter with MA dependence was analyzed.

Results: The mean (sd) methylation levels of CHN2 gene promoter in the case group were significantly higher than in the control group, which were 2795.55 (733.19) and 1026.73 (698.73), respectively, showing significant differences between the two groups (t=21.25, p<0.001). Pearson analysis showed no significant correlation between the methylation levels of CHN2 promoter and other factors (the age of initial MA use, the duration of MA use, combination with K powder, tobacco and alcohol).

Conclusions: The abnormal methylation of CHN2 gene promoter was significantly correlated with MA dependence.

背景: 甲基苯丙胺(Methamphetamine,MA)滥用情况在我国十分严峻,已成为我国第一大毒品。甲基苯丙胺依赖的机制尚不完全清楚。CHN2 基因编码嵌合蛋白-2,该蛋白可通过Rac GTP 酶系统调控轴突修剪,在神经系统功能环路的形成中起关键作用。遗传学研究显示该基因的多态性与物质依赖形成相关。.

目的: 本研究旨在研究CHN2 基因启动子区甲基化改变与甲基苯丙胺依赖的关系,以探索甲基苯丙胺依赖的新机制。.

方法: 采用美国精神障碍诊断与统计手册第四版(DSM-IV)轴I 障碍定式检查工具中文版对强制戒毒所的甲基苯丙胺依赖者进行调查,筛选出224 名男性依赖者纳入病例组。另外选择年龄匹配的109 名身体健康的男性作为对照组。采取受检者静脉血液,采用Methylight qPCR 技术测定CHN2 基因启动子区甲基化状态,统计分析比较两组的检测结果。.

结果: 甲基苯丙胺依赖组CHN2 基因启动子区甲基化程度为2795.55(733.19),显著高于正常对照组的1026.73(698.73),(t=21.25, p<0.001)。相关分析显示CHN2 基因启动子区甲基化程度与开始使用甲基苯丙胺的年龄、使用甲基苯丙胺的总时间、合并使用其它精神活性物质(K 粉、烟草、和酒精)无明显关联。.

结论: CHN2 基因启动子区甲基化改变与甲基苯丙胺依赖显著相关。.

Keywords: CHN2 gene; DNA methylation; Methamphetamine dependence; epigenetic.