Basic Neurosciences, Genetics and Immunology - Original Article

Journal of Neural Transmission

, Volume 116, Issue 5, pp 615-622

N-methyl-d-aspartate 2b receptor subtype (NR2B) promoter methylation in patients during alcohol withdrawal

  • Teresa BiermannAffiliated withDepartment of Psychiatry and Psychotherapy, University Hospital of Erlangen Email author 
  • , Udo ReulbachAffiliated withDepartment of Psychiatry and Psychotherapy, University Hospital of ErlangenDepartment of Epidemiology and Public Health, University College Cork
  • , Bernd LenzAffiliated withDepartment of Psychiatry and Psychotherapy, University Hospital of Erlangen
  • , Helge FrielingAffiliated withDepartment of Psychiatry and Psychotherapy, University Hospital of Erlangen
  • , Marc MuschlerAffiliated withDepartment of Psychiatry, Social Psychiatry and Psychotherapy, Medical School of Hanover
  • , Thomas HillemacherAffiliated withDepartment of Psychiatry, Social Psychiatry and Psychotherapy, Medical School of Hanover
  • , Johannes KornhuberAffiliated withDepartment of Psychiatry and Psychotherapy, University Hospital of Erlangen
  • , Stefan BleichAffiliated withDepartment of Psychiatry, Social Psychiatry and Psychotherapy, Medical School of Hanover

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Abstract

NMDA receptors and especially the NR2B receptor subtype play a crucial role during chronic ethanol consumption and alcohol withdrawal. Therefore, the NR2B receptor subtype expression in peripheral blood cells of 32 male patients suffering from alcohol dependency were assessed through quantitative RT-PCR and to explore regulating epigenetic mechanisms, a methylation analysis was conducted using bisulfite sequencing of a fragment of the NR2B promoter region. The expression of the NR2B receptor increased significantly during the first 24 h of withdrawal treatment (day 1; t = 4.1, P = 0.001), and also on and day 3 (t = 2.4; P = 0.029). The severity of alcohol drinking pattern, measured by lifetime drinking and daily ethanol intake, was negatively correlated with the methylation of a defined cluster of five CPG-sites within the NR2B promoter (lifetime drinking: Spearman’s rho = −0.55; P = 0.013; daily ethanol intake: rho = −0.46; P = 0.043). These findings might explain the observation of an impact of alcohol consumption patterns on the gravity of withdrawal symptoms.

Keywords

Alcoholism NR2B receptor DNA methylation mRNA Alcohol withdrawal