Methamphetamine use disorder (MAUD) can substantially jeopardize public security due to its high-risk social psychology and behaviour. Given that the dopamine reward system is intimately correlated with MAUD, we investigated the association of single nucleotide polymorphisms (SNPs), as well as methylation status of dopamine receptor type 4 (DRD4), catechol-O-methyltransferase (COMT) genes, and paranoid and motor-impulsive symptoms in MAUD patients. A total of 189 MAUD patients participated in our study. Peripheral blood samples were used to detect 3 SNPs and 35 CpG units of methylation in the DRD4 gene promoter region and 5 SNPs and 39 CpG units in the COMT gene. MAUD patients with the DRD4 rs1800955 C allele have a lower percentage of paranoid symptoms than those with the rs1800955 TT allele. Individuals with paranoid symptoms exhibited a reduced methylation degree at a particular DRD4 CpG2.3 unit. The interaction of the DRD4 rs1800955 C allele and the reduced DRD4CpG2.3 methylation degree were associated with a lower occurrence of paranoid symptoms. Meanwhile, those with the COMT rs4818 CC allele had lower motor-impulsivity scores in MAUD patients but greater COMT methylation levels in the promoter region and methylation degree at the COMT CpG 51.52 unit. Therefore, based only on the COMT rs4818 CC polymorphism, there was a negative correlation between COMT methylation and motor-impulsive scores. Our preliminary results provide a clue that the combination of SNP genotype and methylation status of the DRD4 and COMT genes serve as biological indicators for the prevalence of relatively high-risk psychotic symptoms in MAUD patients.

中文翻译：

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多巴胺系统相关基因单核苷酸多态性及甲基化与甲基苯丙胺使用障碍患者精神病症状关系的初步研究

甲基苯丙胺使用障碍（MAUD）因其高风险的社会心理和行为而可能严重危害公共安全。鉴于多巴胺奖赏系统与 MAUD 密切相关，我们研究了单核苷酸多态性 (SNP) 以及多巴胺受体 4 型 (DRD4)、儿茶酚-O-甲基转移酶 (COMT) 基因和偏执狂的甲基化状态之间的关联。 MAUD 患者的运动冲动症状。共有 189 名 MAUD 患者参与了我们的研究。外周血样本检测DRD4基因启动子区甲基化的3个SNP和35个CpG单位，以及COMT基因中的5个SNP和39个CpG单位。携带 DRD4 rs1800955 C 等位基因的 MAUD 患者比携带 rs1800955 TT 等位基因的 MAUD 患者出现偏执症状的比例较低。具有偏执症状的个体在特定 DRD4 CpG2.3 单位表现出甲基化程度降低。 DRD4 rs1800955 C 等位基因和 DRD4CpG2.3 甲基化程度降低的相互作用与偏执症状的发生率降低相关。同时，具有 COMT rs4818 CC 等位基因的 MAUD 患者的运动冲动评分较低，但启动子区域的 COMT 甲基化水平和 COMT CpG 51.52 单位的甲基化程度较高。因此，仅根据 COMT rs4818 CC 多态性，COMT 甲基化与运动冲动评分之间存在负相关。我们的初步结果提供了一条线索，即 SNP 基因型与 DRD4 和 COMT 基因甲基化状态的组合可以作为 MAUD 患者相对高危精神病症状患病率的生物学指标。