Elevated levels of DNA methylation at the OPRM1 promoter in blood and sperm from male opioid addicts
Open accessAbstract
Objective: The OPRM1 gene was studied for DNA methylation in opioid dependence and possible paternal contribution to epigenetic inheritance of altered methylation profiles.Participants and methods: DNA was extracted from blood and sperm from 13 male opioid addicts and 21 male control subjects. DNA methylation was determined by pyrosequencing in 24 CpG sites at the OPRM1 promoter region.Results: The authors found significantly increased overall methylation in blood DNA from addicted subjects (Kruskal-Wallis [K-W] p = 0.013). Seven CpG sites showed significantly hypermethylated blood DNA from cases when compared with blood DNA from controls (p < 0.05 at CpGs 5, 9, 10, 11, 18, 23, and 24). In spermderived DNA from addicts, the methylation was significantly increased at CpG 2 (p = 0.012), and overall methylation did not reach significant difference (K-W p = 0.523).Conclusions: Increased DNA methylation in the OPRM1 gene is associated with opioid dependence. Hypermethylated CpG sites located in OPRM1 promoter may potentially block the binding of Sp1 and other transcription activators, thus leading to OPRM1 silencing. The increased DNA methylation in sperm may suggest a way of epigenetic heritability of opioid abuse or dependence phenotypes.
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Changes in DNA methylation were observed in sperm from men with alcohol or opioid dependence, but effects in offspring were not measured.
“Changes in DNA methylation were observed in sperm from men with alcohol or opioid dependence 199,200 , but effects in offspring were not measured.”
From Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms (2018) · cites this paper as [200]
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- Authors
- Chorbov, P., Todorov, P., Lynskey, P., & Cicero, P.
- Venue
- Journal of Opioid Management
- Publisher
- Weston Medical Publishing
- Published
- 2018-01-15
- Volume
- 7
- Issue
- 4
- Pages
- 258-264
- ISSN
- 1551-7489 (ISSN-L)
- PMC
- PMC4142589
- OpenAlex
- W2325055448
- Cited by
- 135
- References
- 25
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 6 · 2023: 13 · 2022: 11 · 2021: 14 · 2020: 12 · 2019: 15 · 2018: 15 · 2017: 11 · 2016: 7 · 2015: 4 · 2014: 7 · 2013: 1 · 2012: 6
- FWCI
- 1.82
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Opioid Management (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- National Institutes of Health
- National Institute on Alcohol Abuse and Alcoholism (AA017681, K01AA017681)
- National Institute of Mental Health (R01MH083823, MH083823)
- National Institute on Drug Abuse (DA021330, R01DA018823, R01DA021330, DA018823)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Opioid Use Disorder Treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- OPRM1, DNA methylation, promoter hypermethylation, opioid use disorder, sperm DNA methylation, blood DNA methylation, epigenetic inheritance, CpG sites, gene silencing, Sp1
- MeSH terms
- Adult, Analysis of Variance, Heroin Dependence, Humans, Male, Missouri, Opioid-Related Disorders, Pedigree, Promoter Regions, Genetic, Spermatozoa, Up-Regulation, Discriminant Analysis, Case-Control Studies, Sequence Analysis, DNA, Receptors, Opioid, mu, CpG Islands, DNA Methylation, Genetic Predisposition to Disease, Heredity
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