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

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...

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Bibliographic Details
Published in:Journal of Neural Transmission 2009-05, Vol.116 (5), p.615-622
Main Authors: Biermann, Teresa, Reulbach, Udo, Lenz, Bernd, Frieling, Helge, Muschler, Marc, Hillemacher, Thomas, Kornhuber, Johannes, Bleich, Stefan
Format: Article
Language:English
Subjects:
Adult
Alcohol-Induced Disorders, Nervous System - genetics
Alcohol-Induced Disorders, Nervous System - metabolism
Alcohol-Induced Disorders, Nervous System - physiopathology
Alcoholism - genetics
Alcoholism - metabolism
Alcoholism - physiopathology
Basic Neurosciences
Brain - metabolism
Brain - physiopathology
Brain Chemistry - genetics
Cohort Studies
DNA Methylation - genetics
DNA Mutational Analysis
Epigenesis, Genetic - genetics
Gene Silencing - physiology
Genetic Testing
Genetics and Immunology - Original Article
Genotype
Glutamic Acid - metabolism
Humans
Male
Medicine
Medicine & Public Health
Middle Aged
Neurology
Neurosciences
Promoter Regions, Genetic - genetics
Psychiatry
Receptors, N-Methyl-D-Aspartate - genetics
Receptors, N-Methyl-D-Aspartate - metabolism
Substance Withdrawal Syndrome - genetics
Substance Withdrawal Syndrome - metabolism
Substance Withdrawal Syndrome - physiopathology
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Summary: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.
ISSN:0300-9564
1435-1463
DOI:10.1007/s00702-009-0212-2