APBB2 is associated with amphetamine use and plasma beta-amyloids in patients receiving methadone maintenance treatment

Liu, Chia-Chen; Fang, Chiu‐Ping; Liu, Tung‐Hsia; Kuo, Hsin‐Wei; Liu, Shu Chi; Wang, Sheng-Chang; Chen, Andrew C. H.; Liu, Yuli

doi:10.1016/j.pnpbp.2018.01.008

Cited by 7 publications

(5 citation statements)

References 32 publications

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“…Four studies found a significant negative association between amphetamine use disorder or methamphetamine/amphetamine use and opioid abstinence during MOUD treatment [ 58 – 61 ]. The other 4 studies found no significant association [ 54 , 62 – 64 ].…”

Section: Resultsmentioning

confidence: 99%

The impact of methamphetamine/amphetamine use on receipt and outcomes of medications for opioid use disorder: a systematic review

Frost

Lampert

Tsui

et al. 2021

Addict Sci Clin Pract

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Background Methamphetamine/amphetamine use has sharply increased among people with opioid use disorder (OUD). It is therefore important to understand whether and how use of these substances may impact receipt of, and outcomes associated with, medications for OUD (MOUD). This systematic review identified studies that examined associations between methamphetamine/amphetamine use or use disorder and 3 classes of outcomes: (1) receipt of MOUD, (2) retention in MOUD, and (3) opioid abstinence during MOUD. Methods We searched 3 databases (PubMed/MEDLINE, PsycINFO, CINAHL Complete) from 1/1/2000 to 7/28/2020 using key words and subject headings, and hand-searched reference lists of included articles. English-language studies of people with documented OUD/opioid use that reported a quantitative association between methamphetamine/amphetamine use or use disorder and an outcome of interest were included. Study data were extracted using a standardized template, and risk of bias was assessed for each study. Screening, inclusion, data extraction and bias assessment were conducted independently by 2 authors. Study characteristics and findings were summarized for each class of outcomes. Results Thirty-nine studies met inclusion criteria. Studies generally found that methamphetamine/amphetamine use or use disorder was negatively associated with receiving methadone and buprenorphine; 2 studies suggested positive associations with receiving naltrexone. Studies generally found negative associations with retention; most studies finding no association had small samples, and these studies tended to examine shorter retention timeframes and describe provision of adjunctive services to address substance use. Studies generally found negative associations with opioid abstinence during treatment among patients receiving methadone or sustained-release naltrexone implants, though observed associations may have been confounded by other polysubstance use. Most studies examining opioid abstinence during other types of MOUD treatment had small samples. Conclusions Overall, existing research suggests people who use methamphetamine/amphetamines may have lower receipt of MOUD, retention in MOUD, and opioid abstinence during MOUD. Future research should examine how specific policies and treatment models impact MOUD outcomes for these patients, and seek to understand the perspectives of MOUD providers and people who use both opioids and methamphetamine/amphetamines. Efforts to improve MOUD care and overdose prevention strategies are needed for this population.

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Section: Resultsmentioning

confidence: 99%

The impact of methamphetamine/amphetamine use on receipt and outcomes of medications for opioid use disorder: a systematic review

Frost

Lampert

Tsui

et al. 2021

Addict Sci Clin Pract

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“…For instance, KCNQ1, a gene encoding a potassium ion channel, was identified in a GWAS of alcohol dependence ( Edenberg et al, 2010 ; Feng et al, 2022 ). Similarly, APBB2 has been associated with opioid and amphetamine dependence ( Gelernter et al, 2014 ; Liu et al, 2018 ). Among the 5mC overlapping genes, ASIC2 has been linked to addiction-related behavior in mice ( Kreple et al, 2014 ).…”

Section: Discussionmentioning

confidence: 99%

Neuronal-specific methylome and hydroxymethylome analysis reveal significant loci associated with alcohol use disorder

Andrade-Brito,

Núñez-Ríos,

Martínez-Magaña

et al. 2024

Front. Genet.

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Background: Alcohol use disorder (AUD) is a complex condition associated with adverse health consequences that affect millions of individuals worldwide. Epigenetic modifications, including DNA methylation (5 mC), have been associated with AUD and other alcohol-related traits. Epigenome-wide association studies (EWAS) have identified differentially methylated genes associated with AUD in human peripheral and brain tissue. More recently, epigenetic studies of AUD have also evaluated DNA hydroxymethylation (5 hmC) in the human brain. However, most of the epigenetic work in postmortem brain tissue has examined bulk tissue. In this study, we investigated neuronal-specific 5 mC and 5 hmC alterations at CpG sites associated with AUD in the human orbitofrontal cortex (OFC).Methods: Neuronal nuclei from the OFC were evaluated in 34 human postmortem brain samples (10 AUD, 24 non-AUD). Reduced representation oxidative bisulfite sequencing was used to assess 5 mC and 5 hmC at the genome-wide level. Differential 5 mC and 5 hmC were evaluated using the methylKit R package and significance was set at false discovery rate < 0.05 and differential methylation > 2. Functional enrichment analyses were performed, and gene-level convergence was evaluated in an independent dataset that assessed 5 mC and 5 hmC of AUD in bulk cortical tissue.Results: We identified 417 5 mC and 363 5hmC significant differential CpG sites associated with AUD, with 59% in gene promoters. Some of the identified genes have been previously implicated in alcohol consumption, including SYK, DNMT3A for 5 mC, GAD1, DLX1, DLX2, for 5 hmC and GATA4 in both. Convergence with a previous AUD 5 mC and 5 hmC study was observed for 28 genes. We also identified 5 and 35 differential regions for 5 mC and 5 hmC, respectively. Lastly, GWAS enrichment analysis showed an association with AUD for differential 5 mC genes.Discussion: This study reveals neuronal-specific methylome and hydroxymethylome dysregulation associated with AUD, identifying both previously reported and potentially novel gene associations with AUD. Our findings provide new insights into the epigenomic dysregulation of AUD in the human brain.

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“…GWAS studies have suggested an association of APBB2 ( p -value = 1.8 × 10 –9 ) with OUD in African Americans (AA) of two independent samples of the SAGE cohort ( n = 3,318 and n = 1,311) ( 44 ). More recently, variants at APBB2 were also associated amphetamine use in Taiwanese individuals with OUD receiving methadone treatment ( n = 344) ( 45 ). CNIH3 is a glutamate receptor auxiliary protein that regulates trafficking properties in glutamate receptors.…”

Section: Discussionmentioning

confidence: 99%

CpH methylome analysis in human cortical neurons identifies novel gene pathways and drug targets for opioid use disorder

Nagamatsu

Rompala²,

Hurd³

et al. 2023

Front. Psychiatry

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IntroductionDNA methylation (DNAm), an epigenetic mechanism, has been associated with opioid use disorder (OUD) in preclinical and human studies. However, most of the studies have focused on DNAm at CpG sites. DNAm at non-CpG sites (mCpHs, where H indicates A, T, or C) has been recently shown to have a role in gene regulation and to be highly abundant in neurons. However, its role in OUD is unknown. This work aims to evaluate mCpHs in the human postmortem orbital frontal cortex (OFC) in the context of OUD.MethodsA total of 38 Postmortem OFC samples were obtained from the VA Brain Bank (OUD = 12; Control = 26). mCpHs were assessed using reduced representation oxidative bisulfite sequencing in neuronal nuclei. Differential analysis was performed using the “methylkit” R package. Age, ancestry, postmortem interval, PTSD, and smoking status were included as covariates. Significant mCpHs were set at q-value < 0.05. Gene Ontology (GO) and KEGG enrichment analyses were performed for the annotated genes of all differential mCpH loci using String, ShinyGO, and amiGO software. Further, all annotated genes were analyzed using the Drug gene interaction database (DGIdb).ResultsA total of 2,352 differentially methylated genome-wide significant mCpHs were identified in OUD, mapping to 2,081 genes. GO analysis of genes with differential mCpH loci showed enrichment for nervous system development (p-value = 2.32E-19). KEGG enrichment analysis identified axon guidance and glutamatergic synapse (FDR 9E-4–2.1E-2). Drug interaction analysis found 3,420 interactions between the annotated genes and drugs, identifying interactions with 15 opioid-related drugs, including lofexidine and tizanidine, both previously used for the treatment of OUD-related symptoms.ConclusionOur findings suggest a role of mCpHs for OUD in cortical neurons and reveal important biological pathways and drug targets associated with the disorder.

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APBB2 is associated with amphetamine use and plasma beta-amyloids in patients receiving methadone maintenance treatment

Cited by 7 publications

References 32 publications

The impact of methamphetamine/amphetamine use on receipt and outcomes of medications for opioid use disorder: a systematic review

The impact of methamphetamine/amphetamine use on receipt and outcomes of medications for opioid use disorder: a systematic review

Neuronal-specific methylome and hydroxymethylome analysis reveal significant loci associated with alcohol use disorder

CpH methylome analysis in human cortical neurons identifies novel gene pathways and drug targets for opioid use disorder

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