DNA methylation at DLGAP2 and risk for relapse in alcohol dependence during acamprosate treatment.

Autor: Özel F; Department of Organismal Biology, Uppsala University, Uppsala, Sweden; Centre for Women's Mental Health during the Reproductive Lifespan - Womher, Uppsala University, Uppsala, Sweden. Electronic address: fatih.ozel@ebc.uu.se., Di Criscio M; Department of Organismal Biology, Uppsala University, Uppsala, Sweden., Lupu DI; Department of Organismal Biology, Uppsala University, Uppsala, Sweden., Sarkisyan D; Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden., Hlady RA; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota, USA., Robertson KD; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota, USA., Bakalkin G; Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden., Liu Y; MOE Key Laboratory of Metabolism and Molecular Medicine, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences and Zhongshan Hospital, Fudan University, Shanghai, China; State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai, China., Biernacka JM; Department of Psychiatry & Psychology, Mayo Clinic, Rochester, Minnesota, USA., Karpyak VM; Department of Psychiatry & Psychology, Mayo Clinic, Rochester, Minnesota, USA., Ekström TJ; Departments of Clinical Neuroscience and Molecular Medicine and Surgery, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden., Rüegg J; Department of Organismal Biology, Uppsala University, Uppsala, Sweden.
Jazyk: angličtina
Zdroj: Drug and alcohol dependence [Drug Alcohol Depend] 2024 Mar 01; Vol. 256, pp. 111116. Date of Electronic Publication: 2024 Feb 03.
DOI: 10.1016/j.drugalcdep.2024.111116
Abstrakt: Background: Alcohol use disorders are prevalent mental disorders with significant health implications. Epigenetic alterations may play a role in their pathogenesis, as DNA methylation at several genes has been associated with these disorders. We have previously shown that methylation in the DLGAP2 gene, coding for a synaptic density protein, is associated with alcohol dependence. In this study, we aimed to examine the association between DLGAP2 methylation and treatment response among patients undergoing acamprosate treatment.
Methods: 102 patients under acamprosate treatment were included. DNA methylation analysis at DLGAP2 was performed by bisulfite pyrosequencing at the start and after 3-month treatment. Treatment outcomes were having a relapse during the treatment and severity of craving at the end of three months. Cox proportional hazard and linear regression models were performed.
Results: Patients whose methylation levels were decreased during the treatment showed an increased risk for relapse within three months in comparison to the ones without methylation change (hazard ratio [HR]=2.44; 95% confidence interval [CI]=1.04, 5.73; p=0.04). For the same group, a positive association for the severity of craving was observed, yet statistical significance was not reached (β=2.97; 95% CI=-0.41, 6.34; p=0.08).
Conclusion: We demonstrate that patients whose DLGAP2 methylation levels decrease during acamprosate treatment are more likely to relapse compared to the ones without changes. This is in line with our previous findings showing that DLGAP2 methylation is lower in alcohol dependent subjects compared to controls, and might suggest a role for changes in DLGAP2 methylation in treatment response.
Competing Interests: Declaration of Competing Interest None.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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