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

Fatih Özel, Michela Di Criscio, Diana Ioana Lupu, Daniil Sarkisyan, Ryan A. Hlady, Keith D. Robertson, Georgy Bakalkin, Yun Liu, Joanna M. Biernacka, Victor M. Karpyak, Tomas J. Ekström, Joëlle Rüegg

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Article number111116
JournalDrug and Alcohol Dependence
StatePublished - Mar 1 2024


  • Acamprosate
  • Alcohol dependence
  • Alcohol use disorders
  • DLGAP2
  • DNA methylation

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)


Dive into the research topics of 'DNA methylation at DLGAP2 and risk for relapse in alcohol dependence during acamprosate treatment'. Together they form a unique fingerprint.

Cite this