A preliminary study on the association of single nucleotide polymorphisms and methylation of dopamine system‐related genes with psychotic symptoms in patients with methamphetamine use disorder

• Published in: The European journal of neuroscience Vol. 59; no. 7; pp. 1428 - 1440
• Main Authors: Fang, Ting, Liu, Meng‐Nan, Liu, Meng‐Qi, Tian, Xiao‐Yu, Zhang, Xiao‐Jie, Liu, Feng, Hao, Wei, Wu, Ning, Li, Hong, Li, Jin
• Format: Journal Article
• Language: English
• Published: France Wiley Subscription Services, Inc 01.04.2024
• Subjects: Alleles; Catechol; Catechol O-methyltransferase; Catechol O-Methyltransferase - genetics; CpG islands; DNA methylation; Dopamine; Dopamine D4 receptors; dopamine receptor type 4; Gene polymorphism; Genes; Genotype; Humans; Impulsive behavior; Methamphetamine; Methamphetamine - adverse effects; methamphetamine use disorder; Methylation; Methyltransferase; Peripheral blood; Polymorphism, Single Nucleotide; Psychosis; Single-nucleotide polymorphism; Social behavior; catechol‐O‐methyltransferase; dopamine receptor type 4; single nucleotide polymorphism; methylation; methamphetamine use disorder
• ISSN: 0953-816X; 1460-9568
• DOI: 10.1111/ejn.16238

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. The interaction of the DRD4 rs1800955 C allele and the reduced DRD4 CpG2.3 methylation degree were associated with a lower occurrence of paranoid symptoms. Based only on the COMT rs4818 CC polymorphism, there was a negative correlation between COMT methylation and motor‐impulsive scores. The combination of SNP genotype and methylation status of the DRD4 and COMT genes may serve as biological indicators to evaluate the prevalence of relatively high‐risk psychotic symptoms in MAUD patients.