Genetic and Epigenetic Approaches to Opioid Use Disorder.
| Title: | Genetic and Epigenetic Approaches to Opioid Use Disorder. |
|---|---|
| Authors: | Ranadeva ND; Department of Biomedical Science, Faculty of Health Sciences, KIU, Sri Lanka.; Wijekumar PJ; Department of Biomedical Science, Faculty of Health Sciences, KIU, Sri Lanka.; School of Life Sciences, Faculty of Science and Engineering, https://ror.org/0009t4v78Anglia Ruskin University, Cambridge, UK.; Fernando CA; Research and Innovation Division, KIU, Sri Lanka.; Faculty of Graduate Studies, University of Sri Jayewardenepura, Nugegoda, Sri Lanka.; Jayamaha AR; Research and Innovation Division, KIU, Sri Lanka.; Noordeen N; Faculty of Medicine, https://ror.org/02phn5242University of Colombo, Sri Lanka.; Chackrewarthy S; Faculty of Medicine, University of Kelaniya, Sri Lanka.; Fernando N; Faculty of Medical Sciences, University of Sri Jayewardenepura, Sri Lanka. |
| Source: | Expert reviews in molecular medicine [Expert Rev Mol Med] 2025 Sep 25; Vol. 27, pp. e35. Date of Electronic Publication: 2025 Sep 25. |
| Publication Type: | Journal Article; Review |
| Language: | English |
| Journal Info: | Publisher: Published by Cambridge University Press in association with the Clinical and Biomedical Computing Unit of the University of Cambridge School of Clinical Medicine Country of Publication: England NLM ID: 100939725 Publication Model: Electronic Cited Medium: Internet ISSN: 1462-3994 (Electronic) Linking ISSN: 14623994 NLM ISO Abbreviation: Expert Rev Mol Med Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Cambridge, UK : Published by Cambridge University Press in association with the Clinical and Biomedical Computing Unit of the University of Cambridge School of Clinical Medicine, [1997?- |
| MeSH Terms: | Opioid-Related Disorders*/genetics ; Opioid-Related Disorders*/metabolism ; Epigenesis, Genetic* ; Genetic Predisposition to Disease*; Humans ; Animals ; Polymorphism, Single Nucleotide |
| Abstract: | Background: Opioid use disorder (OUD) is a major global-scale social issue affecting public health. The high potential for addiction and dependence makes opioid use a significant concern, contributing to substance-related disorders. Both genetic and environmental factors contribute to the predisposition to OUD, with the opioidergic, dopaminergic, and GABAergic systems playing primary roles in itsonset.; Methods: This narrative review documents the association between genes and their variants related to these three systems, along with current evidence on epigenetic interventions in OUD. Relevant studies investigating candidate-gene associations and molecular mechanisms were synthesized to highlight genetic variants and epigenetic processes linked to OUD.; Results: Genetic associations play a prominent role in OUD, with several single-nucleotide variants identified in affected populations. Key genes implicated include OPRM1, OPRD1, OPRK1, PDYN, OPRL1, and POMC from the opioidergic system; DRD1, DRD2, DRD3, DRD4, ANKK1, and COMT from the dopaminergic system; and GABRA2, GABRB3, GABRG2, GAD1, and GAD2 from the GABAergic system. Evidence also indicates that chronic opioid use is associated with epigenetic changes through posttranslational histone modifications and DNA methylation. However, limitations in existing studies include small sample sizes, limited replication, and potential stratification biases.; Conclusions: Although many candidate-gene associations have been proposed for OUD, robust evidence remains limited. Large, ancestrally diverse genome-wide association studies (GWAS) and systematic replication studies are urgently needed. A deeper understanding of the genetic, epigenetic, and neurobiological bases of addiction will be essential for the development of precisely targeted medications to improve prevention and treatment outcomes for OUD. |
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| Contributed Indexing: | Keywords: DRD2; GAD1; OPRM1; epigenetics; heroin; opioid addiction; opioid use disorder |
| Entry Date(s): | Date Created: 20250924 Date Completed: 20251015 Latest Revision: 20251101 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC12571026 |
| DOI: | 10.1017/erm.2025.10024 |
| PMID: | 40993075 |
| Database: | MEDLINE |
Journal Article; Review