Redefinition of the human kappa opioid receptor gene (OPRK1) structure and association of haplotypes with opiate addiction.
paper
Cited
Public
Unavailable
- Authors
- Yuferov, Vadim; Fussell, David; LaForge, K Steven; Nielsen, David A; Gordon, Derek; Ho, Ann; Leal, Suzanne M; Ott, Jurg; Kreek, Mary Jeanne
- Year
- 2004
- Journal
- Pharmacogenetics
- PMID
- 15608558
- DOI
- 10.1097/00008571-200412000-00002
- PMCID
- PMC6141019
The kappa opioid receptor (KOR) plays a role in stress responsivity, opiate withdrawal and responses to cocaine. KOR activation by its endogenous ligand dynorphin A(1-17) decreases basal and drug-induced striatal levels of dopamine. The complete structure of the human KOR gene (hOPRK1) has not been previously determined. This study: (i) characterized the genomic structure of the hOPRK1 gene; (ii) identified single nucleotide polymorphisms (SNPs) in the hOPRK1 gene; and (iii) investigated possible associations of these variants with vulnerability to develop heroin addiction. Analysis of 5'-RACE cDNA clones revealed the presence of a novel exon 1 ranging in length from 167 to 251 nucleotides in the 5' 5'-untranslated region of the hOPRK1 mRNA. We found that the hOPRK1 gene has four major exons and three introns, similar to rodent OPRK1 genes. Direct sequencing of amplified DNA containing all four exons and intron 1 of the hOPRK1 gene were evaluated for polymorphisms in 291 subjects (145 former heroin addicts and 146 controls). Twelve SNPs were identified, nine novel variants and three previously reported SNPs. Using logistic regression with opioid dependence as the dependent variable, the 36G>T SNP exhibited a point-wise significant association (P = 0.016) with disease status. The number of haplotypes seen in the three ethnic groups were nine, six and five for African-Americans, Caucasians, and Hispanics, respectively, with corresponding significance levels for differences in haplotype frequencies between cases and controls of P = 0.0742, 0.1015 and 0.0041. Combining ethnicities by Fisher's method yields an empirical significance level of P = 0.0020.
No figures extracted from this document.
No chunks β full text not yet ingested.
No entities extracted from this document yet.
No uploaded files.
Not in any collection.
No citations found.
In this knowledge base
External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| Biochemical Diagnosis in Substance and Non-substance Addiction. | Shen W et al. | β | 2025 | β |
| Genetic Associations of Persistent Opioid Use After Surgery Point to OPRM1 but Not Other Opioid-Related Loci as the Main Driver of Opioid Use Disorder. | Annis AC et al. | β | 2025 | β |
| <i>Kappa</i>-opioid receptor gene (<i>OPRK1</i>) variations associated with opioid abstinence behaviors among chronic heroin users. | Greenwald MK et al. | β | 2025 | β |
| Differential methylation of OPRK1 in borderline personality disorder is associated with childhood trauma. | Gescher DM et al. | β | 2024 | β |
| Genetic associations of persistent opioid use after surgery: a hypothesis-driven analysis of high-value genetic variants in the Michigan Genomics Initiative dataset | Brummett C et al. | β | 2023 | β |
| Invited Expert Opinion- Bioinformatic and Limitation Directives to Help Adopt Genetic Addiction Risk Screening and Identify Preaddictive Reward Dysregulation: Required Analytic Evidence to Induce Dopamine Homeostatsis. | Blum K et al. | β | 2023 | β |
| Kappa opioid agonists in the treatment of itch: just scratching the surface? | Beck TC et al. | β | 2023 | β |
| Analyses of polymorphisms of intron 2 of OPRK1 (kappa-opioid receptor gene) in association with opioid and cocaine dependence diagnoses in an African-American population. | Yuferov V et al. | β | 2022 | β |
| Down-regulation of kappa opioid receptor promotes ESCC proliferation, invasion and metastasis via the PDK1-AKT signaling pathway. | Huang HM et al. | β | 2022 | β |
| Kappa Opioid Signaling at the Crossroads of Chronic Pain and Opioid Addiction. | Cahill CM et al. | β | 2022 | β |
| A review of the existing literature on buprenorphine pharmacogenomics. | Meaden CW et al. | β | 2021 | β |
| Bulleyaconitine A Inhibits Morphine-Induced Withdrawal Symptoms, Conditioned Place Preference, and Locomotor Sensitization Via Microglial Dynorphin A Expression. | Zhao MJ et al. | β | 2021 | β |
| Drug Addiction: Hyperkatifeia/Negative Reinforcement as a Framework for Medications Development. | Koob GF | β | 2021 | β |
| Genetic susceptibility of opioid receptor genes polymorphism to drug addiction: A candidate-gene association study. | Al-Eitan LN et al. | β | 2021 | β |
| Overview of Genetic Analysis of Human Opioid Receptors. | Spampinato SM | β | 2021 | β |
| Neuropharmacological and Neurogenetic Correlates of Opioid Use Disorder (OUD) As a Function of Ethnicity: Relevance to Precision Addiction Medicine. | Abijo T et al. | β | 2020 | β |
| Pharmacogenomics of Pain Management: The Impact of Specific Biological Polymorphisms on Drugs and Metabolism. | Cornett EM et al. | β | 2020 | β |
| The Streetlight Effect: Reappraising the Study of Addiction in Light of the Findings of Genome-wide Association Studies. | Hall FS et al. | β | 2020 | β |
| Molecular Imaging of Opioid and Dopamine Systems: Insights Into the Pharmacogenetics of Opioid Use Disorders. | Burns JA et al. | β | 2019 | β |
| Genetic association analyses and meta-analysis of Dynorphin-Kappa Opioid system potential functional variants with heroin dependence. | Yuanyuan J et al. | β | 2018 | β |
| Opioid Receptors Gene Polymorphism and Heroin Dependence in Iran. | Soleimani Asl S et al. | β | 2018 | β |
| Pharmacogenomics Testing for Postoperative Pain Optimization Before Total Knee and Total Hip Arthroplasty. | Awad ME et al. | β | 2018 | β |
| Biochemical Diagnosis in Substance and Non-substance Addiction. | Shen W et al. | β | 2017 | β |
| Drug addiction: An affective-cognitive disorder in need of a cure. | Fattore L et al. | β | 2016 | β |
| Etiological theories of addiction: A comprehensive update on neurobiological, genetic and behavioural vulnerability. | Ouzir M et al. | β | 2016 | β |
| Antidepressant-like effects of buprenorphine in rats are strain dependent. | Browne CA et al. | β | 2015 | β |
| Bioinformatics and evolution of vertebrate nociceptin and opioid receptors. | Stevens CW | β | 2015 | β |
| Variations in opioid receptor genes in neonatal abstinence syndrome. | Wachman EM et al. | β | 2015 | β |
| Association between gene variants and response to buprenorphine maintenance treatment. | Gerra G et al. | β | 2014 | β |
| Genetics and implications in perioperative analgesia. | Trescot AM | β | 2014 | β |
| Genetics of opiate addiction. | Reed B et al. | β | 2014 | β |
| Genetics of Opioid Dependence: A Review of the Genetic Contribution to Opioid Dependence. | Mistry CJ et al. | β | 2014 | β |
| It's MORe exciting than mu: crosstalk between mu opioid receptors and glutamatergic transmission in the mesolimbic dopamine system. | Chartoff EH et al. | β | 2014 | β |
| The association of genetic polymorphisms in the ΞΊ-opioid receptor 1 gene with body weight, alcohol use, and withdrawal symptoms in patients with methadone maintenance. | Wang SC et al. | β | 2014 | β |
| ELK1 transcription factor linked to dysregulated striatal mu opioid receptor signaling network and OPRM1 polymorphism in human heroin abusers. | Daws SE et al. | β | 2013 | β |
| Implications of genome wide association studies for addiction: are our a priori assumptions all wrong? | Hall FS et al. | β | 2013 | β |
| Long-term antagonism of ΞΊ opioid receptors prevents escalation of and increased motivation for heroin intake. | Schlosburg JE et al. | β | 2013 | β |
| NCK2 is significantly associated with opiates addiction in African-origin men. | Liu Z et al. | β | 2013 | β |
| Polymorphisms of the kappa opioid receptor and prodynorphin genes: HIV risk and HIV natural history. | Proudnikov D et al. | β | 2013 | β |
| The ΞΊ-opioid receptor gene as a predictor of response in a cocaine vaccine clinical trial. | Nielsen DA et al. | β | 2013 | β |
| Common and specific liability to addiction: approaches to association studies of opioid addiction. | Nielsen DA et al. | β | 2012 | β |
| Epistatic effects between variants of kappa-opioid receptor gene and A118G of mu-opioid receptor gene increase susceptibility to addiction in Indian population. | Kumar D et al. | β | 2012 | β |
| Stress-induced epigenetic regulation of ΞΊ-opioid receptor gene involves transcription factor c-Myc. | Flaisher-Grinberg S et al. | β | 2012 | β |
| The dynorphin/ΞΊ-opioid receptor system and its role in psychiatric disorders. | Tejeda HA et al. | β | 2012 | β |
| The genetics of the opioid system and specific drug addictions. | Levran O et al. | β | 2012 | β |
| Zebrafish: a model for the study of addiction genetics. | Klee EW et al. | β | 2012 | β |
| ΞΊ-opioid receptor/dynorphin system: genetic and pharmacotherapeutic implications for addiction. | Butelman ER et al. | β | 2012 | β |
| Contribution of cytochrome P450 and ABCB1 genetic variability on methadone pharmacokinetics, dose requirements, and response. | Fonseca F et al. | β | 2011 | β |
| Molecular mechanisms of opioid receptor-dependent signaling and behavior. | Al-Hasani R et al. | β | 2011 | β |
| Transcriptional and epigenetic regulation of opioid receptor genes: present and future. | Wei LN et al. | β | 2011 | β |
| Pharmacogenetics of drug dependence: role of gene variations in susceptibility and treatment. | Khokhar JY 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 |
| Opiate and cocaine addiction: from bench to clinic and back to the bench. | Kreek MJ et al. | β | 2009 | β |
| The evolution of vertebrate opioid receptors. | Stevens CW | β | 2009 | β |
| Addiction and cognitive functions. | Spiga S et al. | β | 2008 | β |
| A regulatory variation in OPRK1, the gene encoding the kappa-opioid receptor, is associated with alcohol dependence. | Edenberg HJ et al. | β | 2008 | β |
| Association between human opioid receptor genes polymorphisms and pressure pain sensitivity in females*. | Huang CJ et al. | β | 2008 | β |
| Association of polymorphisms in the melanocortin receptor type 2 (MC2R, ACTH receptor) gene with heroin addiction. | Proudnikov D et al. | β | 2008 | β |
| Catechol-O-methyltransferase (COMT) gene variants: possible association of the Val158Met variant with opiate addiction in Hispanic women. | Oosterhuis BE et al. | β | 2008 | β |
| Genetic susceptibility to heroin addiction: a candidate gene association study. | Levran O et al. | β | 2008 | β |
| Genotype patterns that contribute to increased risk for or protection from developing heroin addiction. | Nielsen DA et al. | β | 2008 | β |
| Multiple OPR genes influence personality traits in substance dependent and healthy subjects in two American populations. | Luo X et al. | β | 2008 | β |
| Role of a functional human gene polymorphism in stress responsivity and addictions. | Kreek MJ | β | 2008 | β |
| Role of pharmacogenetics in variable response to drugs: focus on opioids. | Kadiev E et al. | β | 2008 | β |
| The OPRD1 and OPRK1 loci in alcohol or drug dependence: OPRD1 variation modulates substance dependence risk. | Zhang H et al. | β | 2008 | β |
| Human kappa opioid receptor gene (OPRK1) polymorphism is associated with opiate addiction. | Gerra G et al. | β | 2007 | β |
| An overview of the genetics of substance use disorders. | Lachman HM | β | 2006 | β |
| Association of the kappa-opioid system with alcohol dependence. | Xuei X et al. | β | 2006 | β |
| Biological research on drug abuse and addiction in Hispanics: current status and future directions. | Trujillo KA et al. | β | 2006 | β |
| Perspectives on current directions in the neurobiology of addiction disorders relevant to genetic risk factors. | Hurd YL | β | 2006 | β |
| Pharmacogenetics of opioid receptors and addiction. | Mayer P et al. | β | 2006 | β |
| Endogenous opiates and behavior: 2004. | Bodnar RJ et al. | β | 2005 | β |
| Genetic influences on impulsivity, risk taking, stress responsivity and vulnerability to drug abuse and addiction. | Kreek MJ et al. | β | 2005 | β |
| Pharmacogenetics and human molecular genetics of opiate and cocaine addictions and their treatments. | Kreek MJ et al. | β | 2005 | β |
| The contribution of genetics to addiction therapy approaches. | Edenberg HJ et al. | β | 2005 | β |