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
{"title":"Associations between methamphetamine use disorder and <i>SLC18A1</i>, <i>SLC18A2</i>, <i>BDNF</i>, and <i>FAAH</i> gene sequence variants and expression levels.","authors":"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","doi":"10.1080/19585969.2024.2413476","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>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: <i>SLC18A1, SLC18A2, BDNF,</i> and <i>FAAH,</i> between controls and people with methamphetamine use disorder.</p><p><strong>Methods: </strong>Fifty-nine participants (29 people with methamphetamine use disorder and 30 controls) completed a clinical interview, cognitive tasks, and provided a blood sample. <i>SLC18A1, SLC18A2, BDNF</i>, and <i>FAAH</i> SNPs were genotyped, and gene expression was assessed with real-time quantitative PCR.</p><p><strong>Results: </strong><i>SLC18A1</i> Pro4Thr was associated with methamphetamine use disorder (OR = 6.22; <i>p</i> = .007). <i>SLC18A2</i> variants, rs363227 and rs363387, were negatively associated with methamphetamine use severity (<i>p</i> = .003) and positively associated with inhibitory control performance (<i>p</i> = .006), respectively. <i>BDNF</i> Val66Met was associated with the severity of use (<i>p</i> = .008). <i>SLC18A2</i> and <i>FAAH</i> mRNA levels were lower in people who use methamphetamine relative to controls (<i>p</i> = .021 and .010, respectively).</p><p><strong>Conclusions: </strong><i>SLC18A1</i> is identified for the first time to play a potential role in methamphetamine use disorder. Lower levels of blood <i>SLC18A2</i> and <i>FAAH</i> 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.</p>","PeriodicalId":54343,"journal":{"name":"Dialogues in Clinical Neuroscience","volume":null,"pages":null},"PeriodicalIF":8.3000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11486062/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Dialogues in Clinical Neuroscience","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/19585969.2024.2413476","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/10/12 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"Medicine","Score":null,"Total":0}
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.
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.