GAD1 but not GAD2 polymorphisms are associated with heroin addiction phenotypes

Shi, Yuhui; Li, Yunxiao; Zhang, Jinyu; Xiao, Yifan; Peng, Yan; Zhu, Yan

doi:10.1016/j.neulet.2019.134704

Cited by 7 publications

(4 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Then, we searched PubMed and Embase for researches related to these SNPs. SNPs that had been reported in previous studies [15][16][17][18][19][20][21] were preferred. Finally, a total of 15 SNPs, including SNPs in Gamma-Aminobutyric Acid Type A Receptor Subunit Alpha 2 (GABRA2; rs11503014, rs279827, rs279858, rs35496835), Gamma-Aminobutyric Acid Type A Receptor Subunit Beta 1 (GABRB1; rs6290, rs1372496, rs4627835, rs16860087), Gamma-Aminobutyric Acid Type A Receptor Subunit Gamma 2 (GABRG2; rs211037, rs11135176, rs209358), Glutamate Decarboxylase 1 (GAD1; rs3749034, rs3791878) and Solute carrier family 1 member 3 (SLC1A3; rs1049524, rs1049522), were genotyped using the Agena MassArray Analyzer 4 system (Agena, USA).…”

Section: Dna Isolation and Genotypingmentioning

confidence: 99%

The Effects of Gene Variations of GABRA2, GABRB1, GABRG2, GAD1 and SLC1A3 on Patients with Propofol During Anesthesia Induction

Zhang¹,

Zheng²,

Ma³

et al. 2021

PGPM

View full text Add to dashboard Cite

Purpose Propofol is one of the most commonly used intravenous sedatives in general anesthesia, while the individual variations of propofol are apparent. The objective of this study was to investigate the influence of genetic variations in GABAergic neurons and glutamatergic neurons on time to loss of consciousness (LOC) and the incidence of hypotension during anesthesia induction. Patients and Methods A total of 140 Chinese patients undergoing thyroid surgery or breast surgery were recruited. Genotyping of candidate genes was carried out using the Agena Bioscience MassARRAY system. Anesthesia induction was initiated with a propofol target plasma concentration (Cp) of 4.0 μg mL −1 . The LOC latency, systolic blood pressure, diastolic blood pressure, mean arterial pressure were documented. Results We found that GABRA2 rs35496835, GABRB1 rs1372496, GABRG2 rs11135176, GABRG2 rs209358, GAD1 rs3791878, SLC1A3 rs1049522 and gender were significant determinants of the patient’s LOC latency following propofol administration. GABRA2 rs11503014 was highly correlated with blood pressure reduction during anesthesia induction. Multiple linear regression analysis revealed that GABRB1 rs1372496, GABRG2 rs11135176, and SLC1A3 rs1049522 accounted for 35.3% variations in LOC latency following propofol administration. Conclusion Our findings indicate that genetic variants of GABRA2, GABRB1, GABRG2, GAD1 and SLC1A3 may have influence on propofol susceptibility, which would be an important guidance towards building clinical models that can precisely predict the efficacy of propofol with various populations before surgery.

show abstract

Section: Dna Isolation and Genotypingmentioning

confidence: 99%

The Effects of Gene Variations of GABRA2, GABRB1, GABRG2, GAD1 and SLC1A3 on Patients with Propofol During Anesthesia Induction

Zhang¹,

Zheng²,

Ma³

et al. 2021

PGPM

View full text Add to dashboard Cite

show abstract

“…The genes interacting with opioids included GRIN1 and OPRK1 , described above. GAD1 is a glutamic acid decarboxylase related to glutamate-dependent acid resistance; candidate gene studies reported genetic variants associated with heroin addiction ( 70 ). KCNH2 , a Potassium Voltage-Gated Channel Subfamily H Member 2, component of potassium channels, was also detected in our study associated with pergolide mesylate, a drug used to treat cocaine dependence ( 71 ).…”

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

View full text Add to dashboard Cite

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.

show abstract

“…The specific mechanisms underlying schizophrenia is still completely unclear, but classical theories believe that serotonin, glutamate, and dopamine networks are closely associated with the onset of schizophrenia [ 49 ]. Glutamate decarboxylase 1 (GAD1) is an important factor in the glutamate metabolism network; it plays a crucial role in conditions such as attention deficit/hyperactivity disorder (ADHD), heroin addiction, early infantile epilepsy, and developmental delay [ 50 , 51 , 52 ]. In patients with schizophrenia, 5mC levels in the promoter region of GAD1 were reduced, resulting in a significant increase in the overall expression of GAD1 [ 37 , 53 ].…”

Section: Altered 5mc Pattern In Schizophreniamentioning

confidence: 99%

Distinctive Patterns of 5-Methylcytosine and 5-Hydroxymethylcytosine in Schizophrenia

Xie,

Wang,

et al. 2024

IJMS

View full text Add to dashboard Cite

Schizophrenia is a highly heritable neuropsychiatric disorder characterized by cognitive and social dysfunction. Genetic, epigenetic, and environmental factors are together implicated in the pathogenesis and development of schizophrenia. DNA methylation, 5-methycytosine (5mC) and 5-hydroxylcytosine (5hmC) have been recognized as key epigenetic elements in neurodevelopment, ageing, and neurodegenerative diseases. Recently, distinctive 5mC and 5hmC pattern and expression changes of related genes have been discovered in schizophrenia. Antipsychotic drugs that affect 5mC status can alleviate symptoms in patients with schizophrenia, suggesting a critical role for DNA methylation in the pathogenesis of schizophrenia. Further exploring the signatures of 5mC and 5hmC in schizophrenia and developing precision-targeted epigenetic drugs based on this will provide new insights into the diagnosis and treatment of schizophrenia.

show abstract

GAD1 but not GAD2 polymorphisms are associated with heroin addiction phenotypes

Cited by 7 publications

References 28 publications

The Effects of Gene Variations of GABRA2, GABRB1, GABRG2, GAD1 and SLC1A3 on Patients with Propofol During Anesthesia Induction

The Effects of Gene Variations of GABRA2, GABRB1, GABRG2, GAD1 and SLC1A3 on Patients with Propofol During Anesthesia Induction

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

Distinctive Patterns of 5-Methylcytosine and 5-Hydroxymethylcytosine in Schizophrenia

Contact Info

Product

Resources

About