{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T05:13:06Z","timestamp":1778130786186,"version":"3.51.4"},"reference-count":51,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:00:00Z","timestamp":1777939200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005984","name":"Dr. Miriam and Sheldon G. Adelson Medical Research Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100005984","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Epigenomes"],"abstract":"<jats:p>Background\/Objectives: Opioid use disorder (OUD) is caused by a complex interplay between genetic and non-genetic factors. DNA methylation is an epigenetic mechanism that modulates gene expression. Data on DNA methylation and opioid addiction and treatment are limited. This association study was designed to assess the difference in genome-wide methylation patterns between individuals with OUD in methadone maintenance treatment (MMT) (n = 114) and those with OUD who achieved long-term abstinence (&gt;10 years) without mu opioid receptor agonist treatment (n = 136). Methods: Differential DNA methylation analysis was performed in whole blood using the Illumina EPIC array. Results: A total of 135 differentially methylated probes (DMPs) reached epigenome-wide significance (p &lt; 1 \u00d7 10\u22127), controlling for sex, age, estimates of blood cell proportions, and the first two principal components based on genome-wide SNP genotypes. The methylation sites were annotated to 157 genes, including 32% long non-coding RNAs. These genes are related to several systems, including cell adhesion (e.g., SAXO4), immune system and inflammation (e.g., UBTF, USP39, C10orf90, PRKCA), stress response (e.g., CRHR1, GPR19), and spermatogenesis (e.g., SPATA16, COX7B2). DMP cg11641410 is located in lncRNA ENSG00000254687, an antisense to OPRK1. Six of the DMPs were also identified in a related longitudinal study of MMT. Conclusions: At this point, it is not possible to determine whether the minor methylation differences observed in this study cause clinically relevant changes in gene expression. However, these findings have the potential to identify biomarkers and to provide new targets for treatment optimization.<\/jats:p>","DOI":"10.3390\/epigenomes10020029","type":"journal-article","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T13:23:37Z","timestamp":1777987417000},"page":"29","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Methadone Maintenance Treatment vs. Long-Term Abstinence Without Opioid Agonist: Epigenome-Wide Study of DNA Methylation"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5136-4184","authenticated-orcid":false,"given":"Orna","family":"Levran","sequence":"first","affiliation":[{"name":"Dr. Miriam & Sheldon G. Adelson Clinic for Drug Abuse Treatment & Research, Tel Aviv Sourasky University Medical Center, Tel Aviv 6423906, Israel"},{"name":"The Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, NY 10065, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justin","family":"Li","sequence":"additional","affiliation":[{"name":"AccuraScience LLC, Johnston, IA 50131, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anat","family":"Sason","sequence":"additional","affiliation":[{"name":"Dr. Miriam & Sheldon G. Adelson Clinic for Drug Abuse Treatment & Research, Tel Aviv Sourasky University Medical Center, Tel Aviv 6423906, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miriam","family":"Adelson","sequence":"additional","affiliation":[{"name":"Dr. Miriam & Sheldon G. Adelson Clinic for Drug Abuse Treatment & Research, Tel Aviv Sourasky University Medical Center, Tel Aviv 6423906, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7091-7987","authenticated-orcid":false,"given":"Einat","family":"Peles","sequence":"additional","affiliation":[{"name":"Dr. Miriam & Sheldon G. Adelson Clinic for Drug Abuse Treatment & Research, Tel Aviv Sourasky University Medical Center, Tel Aviv 6423906, Israel"},{"name":"Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv 6997801, Israel"},{"name":"Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 6997801, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1038\/s41398-024-03119-z","article-title":"Serum cytokines and inflammatory proteins in individuals with heroin use disorder: Potential mechanistically based biomarkers for diagnosis","volume":"14","author":"Butelman","year":"2024","journal-title":"Transl. Psychiatry"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Ray, S., Datta, S., Saha, A., and Sil, S. (2025). Astrocytes and Astrocyte-Derived Extracellular Conduits in Opiate-Mediated Neurological Disorders. 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