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Association of single nucleotide polymorphism and methylation of dopamine system-related genes with psychotic symptoms in patients of methamphetamine use disorders
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  • Ting Fang,
  • Meng-Qi Liu,
  • Meng-Nan Liu,
  • Xiao-Yu Tian,
  • Xiao-Jie Zhang,
  • Feng Liu,
  • Wei Hao,
  • Ning Wu,
  • Hong Li,
  • Jin Li
Ting Fang
Beijing Institute of Pharmacology and Toxicology
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Meng-Qi Liu
The Second Xiangya Hospital of Central South University Department of Blood Transfusion
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Meng-Nan Liu
Beijing Institute of Pharmacology and Toxicology
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Xiao-Yu Tian
Medical School of Chinese PLA
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Xiao-Jie Zhang
The Second Xiangya Hospital of Central South University Department of Blood Transfusion
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Feng Liu
Compulsory detoxification center of Changsha Public Security Bureau
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Wei Hao
The Second Xiangya Hospital of Central South University Department of Blood Transfusion
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Ning Wu
Beijing Institute of Pharmacology and Toxicology
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Hong Li
Beijing Institute of Pharmacology and Toxicology

Corresponding Author:[email protected]

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Jin Li
Beijing Institute of Pharmacology and Toxicology
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Abstract

Background: Methamphetamine use disorders (MAUD) can substantially jeopardize public security due to their high-risk social psychology and behavior. Given that the dopamine reward system is intimately associated with MAUD, we investigated the association of single nucleotide polymorphisms (SNPs), as well as methylation status of DRD4, COMT genes and paranoid, motor impulsive symptoms in MAUD patients. Methods: A total of 189 MAUD patients participated in our study. Samples of peripheral blood were used to detecte for 3 SNPs and levels of 35 CpG units of methylation in the DRD4 gene’s promoter region, 5 SNPs and 39 CpG units in the COMT gene. Results: MAUD patients with rs1800955 C allele have a lower percentage of paranoid symptom than those with rs1800955 TT. Individuals with paranoid symptom exhibited reduced methylation degree at particular DRD4 CpG2.3 unit. The interaction of the DRD4 rs1800955 C allele and the reduced DRD4 CpG2.3 methylation degree resulted in the lower occurrence of the paranoid symptom. Meanwhile, those with COMT rs4818 CC allele have lower motor impulsivity scores in MAUD patients, but greater COMT methylation levels in the promotor region and methylation degree at COMT CpG 51.52 unit. Therefore, based only on COMT rs4818 CC polymorphism, there was a negative correlation between COMT methylation and motor impulsivity scores in the MAUD patients. Conclusions: Our results found that the combination of SNP genotyping 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.
14 Mar 2023Submitted to European Journal of Neuroscience
15 Mar 2023Submission Checks Completed
15 Mar 2023Assigned to Editor
15 Mar 2023Review(s) Completed, Editorial Evaluation Pending
18 Mar 2023Reviewer(s) Assigned
23 Apr 2023Editorial Decision: Revise Major
23 Jun 20231st Revision Received
24 Jun 2023Review(s) Completed, Editorial Evaluation Pending
24 Jun 2023Assigned to Editor
24 Jun 2023Submission Checks Completed
24 Jun 2023Reviewer(s) Assigned
12 Jul 2023Editorial Decision: Revise Minor
03 Oct 20232nd Revision Received
03 Oct 2023Submission Checks Completed
03 Oct 2023Assigned to Editor
03 Oct 2023Review(s) Completed, Editorial Evaluation Pending
03 Oct 2023Reviewer(s) Assigned
14 Oct 2023Editorial Decision: Revise Major
28 Oct 20233rd Revision Received
30 Oct 2023Submission Checks Completed
30 Oct 2023Assigned to Editor
30 Oct 2023Review(s) Completed, Editorial Evaluation Pending
11 Nov 2023Editorial Decision: Revise Minor