Allelic expression imbalance of human mu opioid receptor (OPRM1) caused by variant A118G.
paper
Cited
Public
Unavailable
- Authors
- Zhang, Ying; Wang, Danxin; Johnson, Andrew D; Papp, Audrey C; SadΓ©e, Wolfgang
- Year
- 2005
- Journal
- The Journal of biological chemistry
- PMID
- 16046395
- DOI
- 10.1074/jbc.M504942200
As a primary target for opioid drugs and peptides, the mu opioid receptor (OPRM1) plays a key role in pain perception and addiction. Genetic variants of OPRM1 have been implicated in predisposition to drug addiction, in particular the single nucleotide polymorphism A118G, leading to an N40D substitution, with an allele frequency of 10-32%, and uncertain functions. We have measured allele-specific mRNA expression of OPRM1 in human autopsy brain tissues, using A118G as a marker. In 8 heterozygous samples measured, the A118 mRNA allele was 1.5-2.5-fold more abundant than the G118 allele. Transfection into Chinese hamster ovary cells of a cDNA representing only the coding region of OPRM1, carrying adenosine, guanosine, cytidine, and thymidine in position 118, resulted in 1.5-fold lower mRNA levels only for OPRM1-G118, and more than 10-fold lower OPRM1 protein levels, measured by Western blotting and receptor binding assay. After transfection and inhibition of transcription with actinomycin D, analysis of mRNA turnover failed to reveal differences in mRNA stability between A118 and G118 alleles, indicating a defect in transcription or mRNA maturation. These results indicate that OPRM1-G118 is a functional variant with deleterious effects on both mRNA and protein yield. Clarifying the functional relevance of polymorphisms associated with susceptibility to a complex disorder such as drug addiction provides a foundation for clinical association studies.
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| A common single nucleotide polymorphism A118G of theΒ ΞΌ opioid receptor alters its N-glycosylation and protein stability. | Huang P et al. | β | 2012 | β |
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| Association of polymorphisms of the mu opioid receptor gene with the severity of HIV infection and response to HIV treatment. | Proudnikov D et al. | β | 2012 | β |
| A systematic review of the A118G (Asn40Asp) variant of OPRM1 in relation to smoking initiation, nicotine dependence and smoking cessation. | Verhagen M et al. | β | 2012 | β |
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| Innate immune gene polymorphisms in tuberculosis. | Azad AK et al. | β | 2012 | β |
| Mu opioid receptor (OPRM1) as a predictor of treatment outcome in opiate-dependent individuals of Arab descent. | Al-Eitan LN et al. | β | 2012 | β |
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| Pain intensity the first year after lumbar disc herniation is associated with the A118G polymorphism in the opioid receptor mu 1 gene: evidence of a sex and genotype interaction. | Olsen MB et al. | β | 2012 | β |
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| Propofol increases Β΅-opioid receptor expression in SH-SY5Y human neuroblastoma cells. | Li Z et al. | β | 2012 | β |
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| Testing multiple levels of influence in the intergenerational transmission of alcohol disorders from a developmental perspective: the example of alcohol use promoting peers and ΞΌ-opioid receptor M1 variation. | Chassin L et al. | β | 2012 | β |
| The behavioral, anatomical and pharmacological parallels between social attachment, love and addiction. | Burkett JP et al. | β | 2012 | β |
| The genetics of the opioid system and specific drug addictions. | Levran O et al. | β | 2012 | β |
| The human ΞΌ-opioid receptor gene polymorphism (A118G) is associated with head pain severity in a clinical cohort of female migraine with aura patients. | Menon S et al. | β | 2012 | β |
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| Tobacco smoking produces greater striatal dopamine release in G-allele carriers with mu opioid receptor A118G polymorphism. | Domino EF et al. | β | 2012 | β |
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| Translational genetic approaches to substance use disorders: bridging the gap between mice and humans. | Palmer AA et al. | β | 2012 | β |
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| ΞΊ-opioid receptor/dynorphin system: genetic and pharmacotherapeutic implications for addiction. | Butelman ER et al. | β | 2012 | β |
| ΞΌ-Opioid receptor gene A118G polymorphism predicts survival in patients with breast cancer. | Bortsov AV et al. | β | 2012 | β |
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| An overview of the genetic susceptibility to alcoholism. | Buscemi L et al. | β | 2011 | β |
| Biomarkers to optimize the treatment of nicotine dependence. | Schnoll RA et al. | β | 2011 | β |
| Critical thoughts on current rodent models for evaluating potential treatments of alcohol addiction and withdrawal. | Ripley TL et al. | β | 2011 | β |
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| Evidence for population variation in TSC1 and TSC2 gene expression. | Jentarra GM et al. | β | 2011 | β |
| Evolving knowledge of opioid genetics in cancer pain. | Droney J et al. | β | 2011 | β |
| Functional polymorphism of the mu-opioid receptor gene (OPRM1) influences reinforcement learning in humans. | Lee MR et al. | β | 2011 | β |
| Genetic variability of pain perception and treatment--clinical pharmacological implications. | LΓΆtsch J | β | 2011 | β |
| Human Mu Opioid Receptor (OPRM1 A118G) polymorphism is associated with brain mu-opioid receptor binding potential in smokers. | Ray R et al. | β | 2011 | β |
| Human N-acetyltransferase 1 *10 and *11 alleles increase protein expression through distinct mechanisms and associate with sulfamethoxazole-induced hypersensitivity. | Wang D et al. | β | 2011 | β |
| Intronic polymorphisms affecting alternative splicing of human dopamine D2 receptor are associated with cocaine abuse. | Moyer RA et al. | β | 2011 | β |
| In vitro and ex vivo analysis of CHRNA3 and CHRNA5 haplotype expression. | Doyle GA et al. | β | 2011 | β |
| Micro opioid receptor A118G polymorphism and post-operative pain: opioids' effects on heterozygous patients. | De Capraris A et al. | β | 2011 | β |
| Molecular mechanisms of opioid receptor-dependent signaling and behavior. | Al-Hasani R et al. | β | 2011 | β |
| Next-generation DNA sequencing-based assay for measuring allelic expression imbalance (AEI) of candidate neuropsychiatric disorder genes in human brain. | Xu X et al. | β | 2011 | β |
| No evidence of association between 118A>G OPRM1 polymorphism and heroin dependence in a large Bulgarian case-control sample. | Nikolov MA et al. | β | 2011 | β |
| OPRM1 gene variants modulate amphetamine-induced euphoria in humans. | Dlugos AM et al. | β | 2011 | β |
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| Pharmacological consequence of the A118G ΞΌ opioid receptor polymorphism on morphine- and fentanyl-mediated modulation of CaΒ²βΊ channels in humanized mouse sensory neurons. | Mahmoud S et al. | β | 2011 | β |
| Pilot study examining the frequency of several gene polymorphisms involved in morphine pharmacodynamics and pharmacokinetics in a morbidly obese population. | Lloret Linares C et al. | β | 2011 | β |
| Stress-induced and cue-induced craving for alcohol in heavy drinkers: Preliminary evidence of genetic moderation by the OPRM1 and CRH-BP genes. | Ray LA | β | 2011 | β |
| Structural basis for ΞΌ-opioid receptor binding and activation. | Serohijos AW et al. | β | 2011 | β |
| A118G polymorphism of OPRM1 gene is associated with schizophrenia. | SerΓ½ O et al. | β | 2010 | β |
| Adverse events in analgesic treatment with tramadol associated with CYP2D6 extensive-metaboliser and OPRM1 high-expression variants. | Kim E et al. | β | 2010 | β |
| Allele-specific differences in ryanodine receptor 1 mRNA expression levels may contribute to phenotypic variability in malignant hyperthermia. | Grievink H et al. | β | 2010 | β |
| Allele-specific expression of APC in adenomatous polyposis families. | CastellsaguΓ© E et al. | β | 2010 | β |
| Allelic imbalance (AI) identifies novel tissue-specific cis-regulatory variation for human UGT2B15. | Sun C et al. | β | 2010 | β |
| A novel and rapid method of determining the effect of unclassified MLH1 genetic variants on differential allelic expression. | Perera S et al. | β | 2010 | β |
| Association of human micro-opioid receptor gene polymorphism A118G with fentanyl analgesia consumption in Chinese gynaecological patients. | Zhang W et al. | β | 2010 | β |
| Association of mu-opioid receptor variants and response to citalopram treatment in major depressive disorder. | Garriock HA et al. | β | 2010 | β |
| Association of UGT2B7 and ABCB1 genotypes with morphine-induced adverse drug reactions in Japanese patients with cancer. | Fujita K et al. | β | 2010 | β |
| Genetically determined measures of striatal D2 signaling predict prefrontal activity during working memory performance. | Bertolino A et al. | β | 2010 | β |
| Genetic influences on the dynamics of pain and affect in fibromyalgia. | Finan PH et al. | β | 2010 | β |
| Initial evidence of an association between OPRM1 and adolescent alcohol misuse. | Miranda R et al. | β | 2010 | β |
| Neuropathic and chronic pain stimuli downregulate central mu-opioid and dopaminergic transmission. | Niikura K et al. | β | 2010 | β |
| OPRM1 and CYP2B6 gene variants as risk factors in methadone-related deaths. | Bunten H et al. | β | 2010 | β |
| OPRM1 SNP (A118G): involvement in disease development, treatment response, and animal models. | Mague SD et al. | β | 2010 | β |
| Overview and historical perspective of four papers presented on research related to the endogenous opioid system. | Kreek MJ | β | 2010 | β |
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| Pharmacogenetics of alcohol and alcohol dependence treatment. | Kranzler HR et al. | β | 2010 | β |
| Pharmacogenetics of smoking cessation therapy. | Kortmann GL et al. | β | 2010 | β |
| Polymorphisms of the mu-opioid receptor and dopamine D4 receptor genes and subjective responses to alcohol in the natural environment. | Ray LA et al. | β | 2010 | β |
| Search for genetic markers and functional variants involved in the development of opiate and cocaine addiction and treatment. | Yuferov V et al. | β | 2010 | β |
| Single-nucleotide polymorphism (A118G) in exon 1 of OPRM1 gene causes alteration in downstream signaling by mu-opioid receptor and may contribute to the genetic risk for addiction. | Deb I et al. | β | 2010 | β |
| Subjective responses to alcohol consumption as endophenotypes: advancing behavioral genetics in etiological and treatment models of alcoholism. | Ray LA et al. | β | 2010 | β |
| The interpersonal dimension of borderline personality disorder: toward a neuropeptide model. | Stanley B et al. | β | 2010 | β |
| Trial Protocol: Using genotype to tailor prescribing of nicotine replacement therapy: a randomised controlled trial assessing impact of communication upon adherence. | Marteau TM et al. | β | 2010 | β |
| A common human micro-opioid receptor genetic variant diminishes the receptor signaling efficacy in brain regions processing the sensory information of pain. | Oertel BG et al. | β | 2009 | β |
| A functional haplotype implicated in vulnerability to develop cocaine dependence is associated with reduced PDYN expression in human brain. | Yuferov V et al. | β | 2009 | β |
| A micro opioid receptor gene polymorphism (A118G) and naltrexone treatment response in adherent Korean alcohol-dependent patients. | Kim SG et al. | β | 2009 | β |
| Association between KCNJ6 (GIRK2) gene polymorphisms and postoperative analgesic requirements after major abdominal surgery. | Nishizawa D et al. | β | 2009 | β |
| Association between OPRM1 gene polymorphisms and fentanyl sensitivity in patients undergoing painful cosmetic surgery. | Fukuda K et al. | β | 2009 | β |
| Bidirectional translational research: Progress in understanding addictive diseases. | Kreek MJ et al. | β | 2009 | β |
| Can extremely low or high morphine formation from codeine be predicted prior to therapy initiation? | LΓΆtsch J et al. | β | 2009 | β |
| Cross-sectional analysis of the influence of currently known pharmacogenetic modulators on opioid therapy in outpatient pain centers. | LΓΆtsch J et al. | β | 2009 | β |
| Current evidence for a modulation of low back pain by human genetic variants. | Tegeder I et al. | β | 2009 | β |
| Ethnicity and OPRM variant independently predict pain perception and patient-controlled analgesia usage for post-operative pain. | Tan EC et al. | β | 2009 | β |
| Expansion of the human mu-opioid receptor gene architecture: novel functional variants. | Shabalina SA et al. | β | 2009 | β |
| Functional characterization of human variants of the mu-opioid receptor gene. | Ravindranathan A et al. | β | 2009 | β |
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| Genetic modulation of the pharmacological treatment of pain. | LΓΆtsch J et al. | β | 2009 | β |
| Identification of a Cis-acting regulatory polymorphism in a Eucalypt COBRA-like gene affecting cellulose content. | Thumma BR et al. | β | 2009 | β |
| Meta-analysis of the relevance of the OPRM1 118A>G genetic variant for pain treatment. | Walter C et al. | β | 2009 | β |
| Mouse model of OPRM1 (A118G) polymorphism has sex-specific effects on drug-mediated behavior. | Mague SD et al. | β | 2009 | β |
| Nicotine withdrawal sensitivity, linkage to chr6q26, and association of OPRM1 SNPs in the SMOking in FAMilies (SMOFAM) sample. | Hardin J et al. | β | 2009 | β |
| Now or Later? An fMRI study of the effects of endogenous opioid blockade on a decision-making network. | Boettiger CA et al. | β | 2009 | β |
| OPRM1 Asn40Asp predicts response to naltrexone treatment: a haplotype-based approach. | Oroszi G et al. | β | 2009 | β |
| OPRM1 gene is associated with BMI in Uyghur population. | Xu L et al. | β | 2009 | β |
| Pain-related effects of trait anger expression: neural substrates and the role of endogenous opioid mechanisms. | Bruehl S et al. | β | 2009 | β |
| Pharmacoepigenetic aspects of gene polymorphism on drug therapies: effects of DNA methylation on drug response. | Gomez A et al. | β | 2009 | β |
| Polymorphism of the micro-opioid receptor gene (OPRM1 118A>G) affects fentanyl-induced analgesia during anesthesia and recovery. | Wu WD et al. | β | 2009 | β |
| Promoter polymorphisms in ACE (angiotensin I-converting enzyme) associated with clinical outcomes in hypertension. | Johnson AD et al. | β | 2009 | β |
| Recent advances in the use of opioids for cancer pain. | Droney J et al. | β | 2009 | β |
| Sex heterogeneity in pharmacogenetic smoking cessation clinical trials. | Schnoll RA et al. | β | 2009 | β |
| Stress, alcohol and drug interaction: an update of human research. | Uhart M et al. | β | 2009 | β |
| The G allele of SNP E1/A118G at the mu-opioid receptor gene locus shows genomic evidence of recent positive selection. | Pang GS et al. | β | 2009 | β |
| The interaction of reward genes with environmental factors in contribution to alcoholism in mexican americans. | Du Y et al. | β | 2009 | β |
| Variation in the mu-opioid receptor gene (OPRM1) is associated with dispositional and neural sensitivity to social rejection. | Way BM et al. | β | 2009 | β |
| A functional polymorphism of the micro-opioid receptor gene is associated with completed suicides. | Hishimoto A et al. | β | 2008 | β |
| Allelic mRNA expression of sortilin-1 (SORL1) mRNA in Alzheimer's autopsy brain tissues. | Alachkar H et al. | β | 2008 | β |
| Analgesic requirements after major abdominal surgery are associated with OPRM1 gene polymorphism genotype and haplotype. | Hayashida M et al. | β | 2008 | β |
| An evaluation of mu-opioid receptor (OPRM1) as a predictor of naltrexone response in the treatment of alcohol dependence: results from the Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence (COMBINE) study. | Anton RF et al. | β | 2008 | β |
| Association between single nucleotide polymorphisms in the mu opioid receptor gene (OPRM1) and self-reported responses to alcohol in American Indians. | Ehlers CL et al. | β | 2008 | β |
| Association of ABCB1/MDR1 and OPRM1 gene polymorphisms with morphine pain relief. | Campa D et al. | β | 2008 | β |
| Association of dopamine and opioid receptor genetic polymorphisms with response to methadone maintenance treatment. | Crettol S et al. | β | 2008 | β |
| Candidate gene polymorphisms predicting individual sensitivity to opioids. | Kasai S et al. | β | 2008 | β |
| Differential neural response to alcohol priming and alcohol taste cues is associated with DRD4 VNTR and OPRM1 genotypes. | Filbey FM et al. | β | 2008 | β |
| Differential opioid action on sensory and affective cerebral pain processing. | Oertel BG et al. | β | 2008 | β |
| Dopamine and opioid gene variants are associated with increased smoking reward and reinforcement owing to negative mood. | Perkins KA et al. | β | 2008 | β |
| Drug therapy and personalized health care: pharmacogenomics in perspective. | Sadee W | β | 2008 | β |
| Effects of opioid receptor gene variation on targeted nalmefene treatment in heavy drinkers. | Arias AJ et al. | β | 2008 | β |
| Genetic basis for predicting response to naltrexone in the treatment of alcohol dependence. | Anton RF | β | 2008 | β |
| Genetic contributions to pain: a review of findings in humans. | Fillingim RB et al. | β | 2008 | β |
| Genetic mutations that prevent pain: implications for future pain medication. | Oertel B et al. | β | 2008 | β |
| Genotyping panel for assessing response to cancer chemotherapy. | Dai Z et al. | β | 2008 | β |
| Human expression variation in the mu-opioid receptor is paralleled in rhesus macaque. | Vallender EJ et al. | β | 2008 | β |
| Interindividual variability of methadone response: impact of genetic polymorphism. | Li Y et al. | β | 2008 | β |
| Naltrexone alone and with sertraline for the treatment of alcohol dependence in Alaska natives and non-natives residing in rural settings: a randomized controlled trial. | O'Malley SS et al. | β | 2008 | β |
| Neuroimaging, genetics and the treatment of nicotine addiction. | Ray R et al. | β | 2008 | β |
| Nicotine abstinence-induced cerebral blood flow changes by genotype. | Wang Z et al. | β | 2008 | β |
| Pain genes. | Foulkes T et al. | β | 2008 | β |
| Patterns of evolutionary constraints on genes in humans. | De S et al. | β | 2008 | β |
| Pharmacogenetic insights into codeine analgesia: implications to pediatric codeine use. | Madadi P et al. | β | 2008 | β |
| Pharmacogenetic treatments for drug addiction: alcohol and opiates. | Haile CN et al. | β | 2008 | β |
| Polymorphisms affecting gene transcription and mRNA processing in pharmacogenetic candidate genes: detection through allelic expression imbalance in human target tissues. | Johnson AD et al. | β | 2008 | β |
| Rhesus monkey tryptophan hydroxylase-2 coding region haplotypes affect mRNA stability. | Chen GL et al. | β | 2008 | β |
| Targeting endogenous mu- and delta-opioid receptor systems for the treatment of drug addiction. | Shippenberg TS et al. | β | 2008 | β |
| The mu opioid receptor A118G gene polymorphism moderates effects of trait anger-out on acute pain sensitivity. | Bruehl S et al. | β | 2008 | β |
| Update on neuropharmacological treatments for alcoholism: scientific basis and clinical findings. | Johnson BA | β | 2008 | β |
| Variation at the mu-opioid receptor gene (OPRM1) influences attachment behavior in infant primates. | Barr CS et al. | β | 2008 | β |
| A functional polymorphism of the mu-opioid receptor gene (OPRM1) influences cue-induced craving for alcohol in male heavy drinkers. | van den Wildenberg E et al. | β | 2007 | β |
| Association between single nucleotide polymorphisms in the cannabinoid receptor gene (CNR1) and impulsivity in southwest California Indians. | Ehlers CL et al. | β | 2007 | β |
| Association of the mu-opioid receptor gene with smoking cessation. | MunafΓ² MR et al. | β | 2007 | β |
| CREB1 haplotypes and the relative reinforcing value of nicotine. | Ray R et al. | β | 2007 | β |
| Effect of mu-opioid receptor gene polymorphisms on heroin-induced subjective responses in a Chinese population. | Zhang D et al. | β | 2007 | β |
| Endogenous opioid blockade and impulsive responding in alcoholics and healthy controls. | Mitchell JM et al. | β | 2007 | β |
| Genetics and smoking cessation improving outcomes in smokers at risk. | Lerman CE et al. | β | 2007 | β |
| KCNMB1 genotype influences response to verapamil SR and adverse outcomes in the INternational VErapamil SR/Trandolapril STudy (INVEST). | Beitelshees AL et al. | β | 2007 | β |
| Mechanistic role of a disease-associated genetic variant within the ADAM33 asthma susceptibility gene. | Del Mastro RG et al. | β | 2007 | β |
| micro-Opioid receptor activation prevents acute hepatic inflammation and cell death. | Chakass D et al. | β | 2007 | β |
| Modulation of Ca2+ channels by heterologously expressed wild-type and mutant human micro-opioid receptors (hMORs) containing the A118G single-nucleotide polymorphism. | Margas W et al. | β | 2007 | β |
| [N-allyl-Dmt1]-endomorphins are micro-opioid receptor antagonists lacking inverse agonist properties. | Marczak ED et al. | β | 2007 | β |
| Opioid receptor gene (OPRM1, OPRK1, and OPRD1) variants and response to naltrexone treatment for alcohol dependence: results from the VA Cooperative Study. | Gelernter J et al. | β | 2007 | β |
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| Pharmacogenetics of opioids. | Somogyi AA et al. | β | 2007 | β |
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| Polymorphisms in the mu-opioid receptor gene (OPRM1) and the implications for alcohol dependence in humans. | van der Zwaluw CS et al. | β | 2007 | β |
| Population-specific effects of the Asn40Asp polymorphism at the mu-opioid receptor gene (OPRM1) on HPA-axis activation. | Hernandez-Avila CA et al. | β | 2007 | β |
| Single nucleotide polymorphisms of the DNA repair gene XPD/ERCC2 alter mRNA expression. | Wolfe KJ et al. | β | 2007 | β |
| The Asp40 mu-opioid receptor allele does not predict naltrexone treatment efficacy in heavy drinkers. | Mitchell JM et al. | β | 2007 | β |
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