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- Meng, Weida, et al.
(författare)
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Genotype-dependent epigenetic regulation of DLGAP2 in alcohol use and dependence
- 2021
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Ingår i: Molecular Psychiatry. - : Springer Nature. - 1359-4184 .- 1476-5578. ; 26:8, s. 4367-4382
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Tidskriftsartikel (refereegranskat)abstract
- Alcohol misuse is a major public health problem originating from genetic and environmental risk factors. Alterations in the brain epigenome may orchestrate changes in gene expression that lead to alcohol misuse and dependence. Through epigenome-wide association analysis of DNA methylation from human brain tissues, we identified a differentially methylated region, DMR-DLGAP2, associated with alcohol dependence. Methylation within DMR-DLGAP2 was found to be genotype-dependent, allele-specific and associated with reward processing in brain. Methylation at the DMR-DLGAP2 regulated expression of DLGAP2 in vitro, and Dlgap2-deficient mice showed reduced alcohol consumption compared with wild-type controls. These results suggest that DLGAP2 may be an interface for genetic and epigenetic factors controlling alcohol use and dependence.
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| 2. |
- Özel, Fatih, et al.
(författare)
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DNA methylation at DLGAP2 and risk for relapse in alcohol dependence during acamprosate treatment
- 2024
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Ingår i: Drug And Alcohol Dependence. - : Elsevier. - 0376-8716 .- 1879-0046. ; 256
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Tidskriftsartikel (refereegranskat)abstract
- 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 (beta=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.
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