Associations between methamphetamine use disorder and SLC18A1, SLC18A2, BDNF, and FAAH gene sequence variants and expression levels.

IF 8.3 2区医学 Q1 Medicine

Dialogues in Clinical Neuroscience Pub Date : 2024-01-01 Epub Date: 2024-10-12 DOI:10.1080/19585969.2024.2413476

Alexandre A Guerin, Briana Spolding, Kiymet Bozaoglu, Courtney Swinton, Zoe Liu, Bruna Panizzutti Parry, Trang Truong, Brian Dean, Andrew J Lawrence, Yvonne Bonomo, Eric J Nestler, Peter J Hamilton, Michael Berk, Susan Rossell, Ken Walder, Jee Hyun Kim

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引用次数: 0

Abstract

Introduction: Assessing candidate gene sequence variations and expression helps to understand methamphetamine use disorder and inform potential treatments. We investigated single nucleotide polymorphisms (SNPs) and gene expression in four candidate genes: SLC18A1, SLC18A2, BDNF, and FAAH, between controls and people with methamphetamine use disorder.

Methods: Fifty-nine participants (29 people with methamphetamine use disorder and 30 controls) completed a clinical interview, cognitive tasks, and provided a blood sample. SLC18A1, SLC18A2, BDNF, and FAAH SNPs were genotyped, and gene expression was assessed with real-time quantitative PCR.

Results: SLC18A1 Pro4Thr was associated with methamphetamine use disorder (OR = 6.22; p = .007). SLC18A2 variants, rs363227 and rs363387, were negatively associated with methamphetamine use severity (p = .003) and positively associated with inhibitory control performance (p = .006), respectively. BDNF Val66Met was associated with the severity of use (p = .008). SLC18A2 and FAAH mRNA levels were lower in people who use methamphetamine relative to controls (p = .021 and .010, respectively).

Conclusions: SLC18A1 is identified for the first time to play a potential role in methamphetamine use disorder. Lower levels of blood SLC18A2 and FAAH mRNA in people with methamphetamine use disorder suggest reduced monoamine reuptake, recycling, or release, and higher anandamide levels in this clinical group, which may be potential therapeutic targets.

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甲基苯丙胺使用障碍与 SLC18A1、SLC18A2、BDNF 和 FAAH 基因序列变异和表达水平之间的关系。

导言：评估候选基因的序列变异和表达有助于了解甲基苯丙胺使用障碍，并为潜在的治疗方法提供信息。我们研究了四个候选基因的单核苷酸多态性（SNPs）和基因表达：SLC18A1、SLC18A2、BDNF 和 FAAH：59名参与者（29名甲基苯丙胺使用障碍患者和30名对照组）完成了临床访谈、认知任务并提供了血液样本。对 SLC18A1、SLC18A2、BDNF 和 FAAH SNPs 进行基因分型，并用实时定量 PCR 评估基因表达：结果：SLC18A1 Pro4Thr与甲基苯丙胺使用障碍有关（OR = 6.22; p = .007）。SLC18A2变体rs363227和rs363387分别与甲基苯丙胺使用严重程度呈负相关（p = .003），与抑制控制能力呈正相关（p = .006）。BDNF Val66Met 与使用甲基苯丙胺的严重程度相关（p = .008）。与对照组相比，吸食甲基苯丙胺者的SLC18A2和FAAH mRNA水平较低（p = .021和.010）：结论：SLC18A1首次被确认在甲基苯丙胺使用障碍中发挥潜在作用。甲基苯丙胺使用障碍患者血液中 SLC18A2 和 FAAH mRNA 含量较低，这表明该临床群体中单胺再摄取、再循环或释放减少，而苯丙胺含量较高，这可能是潜在的治疗目标。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Dialogues in Clinical Neuroscience Medicine-Psychiatry and Mental Health

CiteScore

19.30

自引率

1.20%

发文量

期刊介绍： Dialogues in Clinical Neuroscience (DCNS) endeavors to bridge the gap between clinical neuropsychiatry and the neurosciences by offering state-of-the-art information and original insights into pertinent clinical, biological, and therapeutic aspects. As an open access journal, DCNS ensures accessibility to its content for all interested parties. Each issue is curated to include expert reviews, original articles, and brief reports, carefully selected to offer a comprehensive understanding of the evolving landscape in clinical neuroscience. Join us in advancing knowledge and fostering dialogue in this dynamic field.