ArticlePharmacogenetics2004
Redefinition of the human kappa opioid receptor gene (OPRK1) structure and association of haplotypes with opiate addiction.
Article in Pharmacogenetics, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 127 citations in OpenAlex.
- The κ-opioid receptor gene as a predictor of response in a cocaine vaccine clinical trial.Psychiatric genetics · 2013Trial
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- 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.Genetic epidemiology · 2025Article
- Differential methylation of OPRK1 in borderline personality disorder is associated with childhood trauma.Molecular psychiatry · 2024Article
- 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.Medical research archives · 2023Article
- Down-regulation of kappa opioid receptor promotes ESCC proliferation, invasion and metastasis via the PDK1-AKT signaling pathway.Cell communication and signaling : CCS · 2022Article
- Kappa Opioid Signaling at the Crossroads of Chronic Pain and Opioid Addiction.Handbook of experimental pharmacology · 2022Article
- A review of the existing literature on buprenorphine pharmacogenomics.The pharmacogenomics journal · 2021Review
- Genetic susceptibility of opioid receptor genes polymorphism to drug addiction: A candidate-gene association study.BMC psychiatry · 2021Article
- Drug Addiction: Hyperkatifeia/Negative Reinforcement as a Framework for Medications Development.Pharmacological reviews · 2021Review
- Bulleyaconitine A Inhibits Morphine-Induced Withdrawal Symptoms, Conditioned Place Preference, and Locomotor Sensitization Via Microglial Dynorphin A Expression.Frontiers in pharmacology · 2021Article
- Pharmacogenomics of Pain Management: The Impact of Specific Biological Polymorphisms on Drugs and Metabolism.Current oncology reports · 2020Review
- Neuropharmacological and Neurogenetic Correlates of Opioid Use Disorder (OUD) As a Function of Ethnicity: Relevance to Precision Addiction Medicine.Current neuropharmacology · 2020Review
- Molecular Imaging of Opioid and Dopamine Systems: Insights Into the Pharmacogenetics of Opioid Use Disorders.Frontiers in psychiatry · 2019Review
- Variations in opioid receptor genes in neonatal abstinence syndrome.Drug and alcohol dependence · 2015Article
- Antidepressant-like effects of buprenorphine in rats are strain dependent.Behavioural brain research · 2015Article
- Genetics of opiate addiction.Current psychiatry reports · 2014Review
- Genetics of Opioid Dependence: A Review of the Genetic Contribution to Opioid Dependence.Current psychiatry reviews · 2014Article
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
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.
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