Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The role of the Asn40Asp polymorphism of the mu opioid receptor gene (OPRM1) on alcoholism etiology and treatment: a critical review.

ABSTRACT: The endogenous opioid system has been implicated in the pathophysiology of alcoholism as it modulates the neurobehavioral effects of alcohol. A variant in the mu opioid receptor gene (OPRM1), the Asn40Asp polymorphism, has received attention as a functional variant that may influence a host of behavioral phenotypes for alcoholism as well as clinical response to opioid antagonists. This paper will review converging lines of evidence on the effect of the Asn40Asp SNP on alcoholism phenotypes, including: (i) genetic association studies; (ii) behavioral studies of alcoholism; (iii) neuroimaging studies; (iv) pharmacogenetic studies and clinical trials; and (v) preclinical animal studies. Together, these lines of research seek to elucidate the effects of this functional polymorphism on alcoholism etiology and treatment response.

SUBMITTER: Ray LA

PROVIDER: S-EPMC3249007 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

The role of the Asn40Asp polymorphism of the mu opioid receptor gene (OPRM1) on alcoholism etiology and treatment: a critical review.

Ray Lara A LA Barr Christina S CS Blendy Julie A JA Oslin David D Goldman David D Anton Raymond F RF

Alcoholism, clinical and experimental research 20110906 3

The endogenous opioid system has been implicated in the pathophysiology of alcoholism as it modulates the neurobehavioral effects of alcohol. A variant in the mu opioid receptor gene (OPRM1), the Asn40Asp polymorphism, has received attention as a functional variant that may influence a host of behavioral phenotypes for alcoholism as well as clinical response to opioid antagonists. This paper will review converging lines of evidence on the effect of the Asn40Asp SNP on alcoholism phenotypes, incl ...[more]

PMID: 21895723

Similar Datasets

μ-Opioid receptor gene (OPRM1) polymorphism in patients with breast cancer.

Project description:Structure-dependent μ-opioid receptor (MOR) activity is an important element in cancer opioid analgesic effectiveness. It is widely accepted that guanine (G) substitution for adenine (A) at OPRM1 gene sequence position 118 changes receptor glycosylation pattern. This is associated with decreased binding ability in both exogenous and endogenous opioids, resulting in increased human pain resistance. The endogenous opioid system's function in body homeostasis maintenance is considered mainly regulatory, so its participation in breast tumor formation and progression is identified herein. We examine the association of the most frequent MOR (A118G) gene polymorphism on breast cancer risk in a Northeastern Polish population by PCR-RFLP comparison of A and G allele frequency at OPRM1 gene A118G polymorphic site in breast cancer-diagnosed patients with healthy control group frequencies. Our results highlight a strong association between G allele presence at μ-opioid receptor A118G and increased breast cancer incidence (OR = 3.3, 95 % CI 2.2-5.0, p < 0.0001) and female gender (OR = 2.0, 95 % CI 1.4-2.9, p = 0.0004). Consequently, OPRM1 G allele presence at that site is a highly significant risk factor in breast cancer development.

| S-EPMC4529459 | biostudies-literature

Characterization of mu opioid receptor cells in a new Oprm1-cre mouse

Project description:we derived, validated, and applied a novel MOR-specific Cre mouse line, inserting a T2A cleavable peptide sequence and the Cre coding sequence into the MOR 3’UTR. Importantly, this line shows specificity and fidelity of MOR expression throughout the brain and with respect to function, there were no differences in behavioral responses to morphine when compared to wild type mice, nor are there any alterations in Oprm1 gene expression or receptor density. To assess Cre recombinase activity, MOR-Cre mice were crossed with the floxed GFP-reporters, RosaLSLSun1-sfGFP or RosaLSL-GFP-L10a. The latter allowed for cell type specific RNA sequencing via TRAP (Translating Ribosome Affinity Purification) of striatal MOR+ neurons following opioid withdrawal.

2023-01-01 | GSE218564 | GEO

Opioid receptor mu 1 (OPRM1) A118G polymorphism (rs1799971) and postoperative nausea and vomiting.

Project description:BACKGROUND:OPRM1-A118G polymorphism (A > G, rs1799971) is associated with interindividual variability in both response to postoperative pain and opioid treatment. The aim of this meta-analysis is to identify the predictive strength in the current literature of OPRM1-A118G polymorphism to postoperative anesthetic reactions, including nausea, vomiting, pruritus and dizziness. METHODS:PubMed, EMBASE, Cochrane Library, Web of Knowledge, Google Scholar and CNKI database were searched to find gene-association researches exploring the impacts of OPRM1-A118G polymorphism on postoperative side effects (time: up to July 2016). Odd ratios (ORs) with 95% confidence intervals (95% CIs) were estimated in allele model, homozygote model, heterozygote model, dominant model and recessive model. Sensitivity analysis and potential bias were also assessed. RESULTS:137 articles were retrieved from databases. 17 eligible studies, including 4690 patients were considered in the meta-analysis. The ORs with 95% CIs of postoperative nausea, vomiting, nausea and vomiting (PONV), pruritus and dizziness in the five genetic models mentioned above were determined. Postoperative vomiting was significantly associated with OPRM1-A118G polymorphism in homozygote (OR: 0.422; 95% CI: 0.254, 0.701; P = 0.001), dominant (OR: 0.765; 95% CI: 0.592, 0.987; P = 0.040) and recessive (OR: 0.439; 95% CI: 0.268, 0.717; P = 0.001) models. The 118G allele was associated with a reduced risk of vomiting. No other associations were detected. There was no evidence of publication bias. CONCLUSIONS:OPRM1-A118G polymorphism (A > G) is associated with a reduced risk of postoperative vomiting, but not nausea, pruritus and dizziness. The results should be interpreted with caution due to limited sample and possible heterogeneity between the included studies. Well-designed and large-scale studies are necessary to confirm our results.

| S-EPMC6176240 | biostudies-literature

Association of opioid receptor mu 1 (OPRM1) A118G polymorphism (rs1799971) with nicotine dependence.

Project description:Background and objectWhether opioid-receptor mu 1 (OPRM1) A118G polymorphism (rs1799971) is associated with nicotine dependence is controversial. We analyzed the combined results from published studies of this possibility.MethodsLiterature reviews were performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Web of Science, Chinese National Science Infrastructure (CNKI), PubMed, Embase and Google Scholar database searches using MeSH terms were conducted to find all relevant researches up to October 2016. Odds ratios (ORs) and their 95% confidence intervals (95% CIs) were calculated in allele, homozygote, heterozygote, dominant and recessive models. Ethnicity-specific subgroup meta-analysis, heterogeneity, sensitivity analysis and publication bias were considered.ResultsSeven eligible studies with 3313 patients were included. The ORs in the five genetic models mentioned above were 1.000 (95% CI: 0.906, 1.104; p = 0.999), 1.032 (95% CI: 0.771, 1.381; p = 0.834), 0.963 (95% CI: 0.799, 1.162; p = 0.696), 1.006 (95% CI: 0.916, 1.104; p = 0.907), 0.967 (95% CI: 0.715, 1.309; p = 0.830), respectively. Only in dominant model is the association significant. Upon ethnicity-specific subgroup analysis, there is no statistical significance.ConclusionOPRM1-A118G polymorphism (A>G) is not associated with nicotine dependence.

| S-EPMC5663599 | biostudies-literature

Subjective response to alcohol among alcohol-dependent individuals: effects of the μ-opioid receptor (OPRM1) gene and alcoholism severity.

Project description:Subjective response to alcohol has been examined as a marker of alcoholism risk. The A118G single-nucleotide polymorphism (SNP) of the mu-opioid receptor (OPRM1) gene has been previously associated with subjective response to alcohol in heavy drinkers. This study seeks to extend the literature by examining the effect of OPRM1 genotype on responses to alcohol in a sample of alcohol-dependent individuals. A secondary aim of this study is to examine alcoholism severity as a predictor of subjective responses to alcohol.Nontreatment seeking problem drinkers (n = 295) were assessed in the laboratory for clinical dimensions of alcohol dependence. Following prospective genotyping, 43 alcohol-dependent individuals across the 2 genotype conditions (AA, n = 23 and AG/GG, n = 20) were randomized to 2 intravenous infusion sessions: 1 of alcohol (target breath alcohol concentration = 0.06 g/dl) and 1 of saline. Measures of subjective responses to alcohol were administered in both infusion sessions.Alcohol-dependent G-allele carriers reported greater alcohol-induced stimulation, vigor, and positive mood, as compared to A-allele homozygotes. There was no genotype effect on alcohol-induced sedation or craving. There was a statistical trend-level severity × alcohol interaction such that individuals at higher levels of severity reported greater alcohol-induced tension reduction.These results support the hypothesis that OPRM1 genotype moderates the hedonic effects of alcohol, but not the sedative and unpleasant effects of alcohol, in a sample of alcohol-dependent patients. Results are discussed in light of a clinical neuroscience framework to alcoholism.

| S-EPMC3548029 | biostudies-other

Functional polymorphism of the mu-opioid receptor gene (OPRM1) influences reinforcement learning in humans.

Project description:Previous reports on the functional effects (i.e., gain or loss of function), and phenotypic outcomes (e.g., changes in addiction vulnerability and stress response) of a commonly occurring functional single nucleotide polymorphism (SNP) of the mu-opioid receptor (OPRM1 A118G) have been inconsistent. Here we examine the effect of this polymorphism on implicit reward learning. We used a probabilistic signal detection task to determine whether this polymorphism impacts response bias to monetary reward in 63 healthy adult subjects: 51 AA homozygotes and 12 G allele carriers. OPRM1 AA homozygotes exhibited typical responding to the rewarded response--that is, their bias to the rewarded stimulus increased over time. However, OPRM1 G allele carriers exhibited a decline in response to the rewarded stimulus compared to the AA homozygotes. These results extend previous reports on the heritability of performance on this task by implicating a specific polymorphism. Through comparison with other studies using this task, we suggest a possible mechanism by which the OPRM1 polymorphism may confer reduced response to natural reward through a dopamine-mediated decrease during positive reinforcement learning.

| S-EPMC3166306 | biostudies-literature

Alternative Pre-mRNA Splicing of the Mu Opioid Receptor Gene, OPRM1: Insight into Complex Mu Opioid Actions.

Project description:Most opioid analgesics used clinically, including morphine and fentanyl, as well as the recreational drug heroin, act primarily through the mu opioid receptor, a class A Rhodopsin-like G protein-coupled receptor (GPCR). The single-copy mu opioid receptor gene, OPRM1, undergoes extensive alternative splicing, creating multiple splice variants or isoforms via a variety of alternative splicing events. These OPRM1 splice variants can be categorized into three major types based on the receptor structure: (1) full-length 7 transmembrane (TM) C-terminal variants; (2) truncated 6TM variants; and (3) single TM variants. Increasing evidence suggests that these OPRM1 splice variants are pharmacologically important in mediating the distinct actions of various mu opioids. More importantly, the OPRM1 variants can be targeted for development of novel opioid analgesics that are potent against multiple types of pain, but devoid of many side-effects associated with traditional opiates. In this review, we provide an overview of OPRM1 alternative splicing and its functional relevance in opioid pharmacology.

| S-EPMC8534031 | biostudies-literature

Cortisol Stress Response in Men and Women Modulated Differentially by the Mu-Opioid Receptor Gene Polymorphism OPRM1 A118G.

Project description:Differences in stress reactivity may affect long-term health outcomes, but there is little information on how these differences arise. The stress axis is regulated by, in part, the endogenous opioid, beta-endorphin, acting on mu-opioid receptors. Persons carrying one or two copies of the G allele of the mu-opioid receptor gene (OPRM1 A118G) may have higher receptor binding for beta-endorphin compared with AA homozygotes that may contribute to individual differences in cortisol reactivity to stress, leading to a relative blunting of cortisol stress reactivity in G allele genotypes. We measured cortisol in 251 young adults (69 GA/GG vs 182 AA genotypes) exposed to mental arithmetic plus public speaking stress relative to a resting control day. Women had smaller cortisol responses than men (F=10.2, p=0.002), and women with GA or GG genotypes (N=39) had an absence of cortisol response relative to AA carriers (N=110) (F=18.4, p<0.0001). Male genotypes had no such difference in response (F=0.29). Cortisol response following mu-opioid receptor blockade using naltrexone in 119 of these subjects unmasked a greater tonic opioid inhibition of cortisol secretion in women (N=64), consistent with their blunted stress reactivity. Compared with men, women may have cortisol stress responses that are more heavily regulated by endogenous opioid mechanisms, and the OPRM1 GA/GG genotypes may affect females differentially relative to males. Diminished cortisol responses to stress may have consequences for health behaviors in women with GA/GG genotypes.

| S-EPMC4569944 | biostudies-literature

Bioinformatic analysis of the human mu opioid receptor (OPRM1) splice and polymorphic variants.

Project description:Mu opioid receptor (OPRM1), a member of the G-protein coupled receptor superfamily, mediates the analgesic and euphoric effects of opioid drugs. The sequences of OPRM1 cDNA and reported splice variants were used to search the public and Celera genomic databases. The matched sequences were analyzed to assemble an OPRM1 genomic contig. Human OPRM1 gene was estimated to span at least 90 kb in the chromosome 6q24-25 region. Four coding exons are separated by 3 introns. While intron 2 has only 773 bp, these databases for the first time provide the precise length of and other information about long introns 1 and 3, containing 50 and 27 kb, respectively. When a consensus exon/intron splice junction at the end of the coding exon 3 was not utilized, it may have resulted in continuous translation of the exon to yield the splice variant OPRM1A. The study did not identify human orthologs of other OPRM1 variants that had been reported for mouse OPRM1, although several proposed exons were found to be included in mouse genomic clones. Single nucleotide polymorphisms in the OPRM1 gene were also analyzed and summarized, which could provide potential polymorphic markers for molecular genetic studies.

| S-EPMC2751312 | biostudies-other

ELK1 transcription factor linked to dysregulated striatal mu opioid receptor signaling network and OPRM1 polymorphism in human heroin abusers.

Project description:BACKGROUND:Abuse of heroin and prescription opiate medications has grown to disturbing levels. Opioids mediate their effects through mu opioid receptors (MOR), but minimal information exists regarding MOR-related striatal signaling relevant to the human condition. The striatum is a structure central to reward and habitual behavior and neurobiological changes in this region are thought to underlie the pathophysiology of addiction disorders. METHODS:We examined molecular mechanisms related to MOR in postmortem human brain striatal specimens from a homogenous European Caucasian population of heroin abusers and control subjects and in an animal model of heroin self-administration. Expression of ets-like kinase 1 (ELK1) was examined in relation to polymorphism of the MOR gene OPRM1 and drug history. RESULTS:A characteristic feature of heroin abusers was decreased expression of MOR and extracellular regulated kinase signaling networks, concomitant with dysregulation of the downstream transcription factor ELK1. Striatal ELK1 in heroin abusers associated with the polymorphism rs2075572 in OPRM1 in a genotype dose-dependent manner and correlated with documented history of heroin use, an effect reproduced in an animal model that emphasizes a direct relationship between repeated heroin exposure and ELK1 dysregulation. A central role of ELK1 was evidenced by an unbiased whole transcriptome microarray that revealed ~20% of downregulated genes in human heroin abusers are ELK1 targets. Using chromatin immune precipitation, we confirmed decreased ELK1 promoter occupancy of the target gene Use1. CONCLUSIONS:ELK1 is a potential key transcriptional regulatory factor in striatal disturbances associated with heroin abuse and relevant to genetic mutation of OPRM1.

| S-EPMC4070524 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data