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-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.
Biermann
Teresa
T
Department of Psychiatry and Psychotherapy, University Hospital of Erlangen, Erlangen, Germany. teresa.biermann@uk-erlangen.de
Reulbach
Udo
U
Lenz
Bernd
B
Frieling
Helge
H
Muschler
Marc
M
Hillemacher
Thomas
T
Kornhuber
Johannes
J
Bleich
Stefan
S
D000328:Adult; D020268:Alcohol-Induced Disorders, Nervous System / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D000437:Alcoholism / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D001921:Brain / Q000378:metabolism / Q000503:physiopathology; D001923:Brain Chemistry / Q000235:genetics; D015331:Cohort Studies; D019175:DNA Methylation / Q000235:genetics*; D004252:DNA Mutational Analysis; D044127:Epigenesis, Genetic / Q000235:genetics; D020868:Gene Silencing / Q000502:physiology; D005820:Genetic Testing; D005838:Genotype; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic / Q000235:genetics*; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics* / Q000378:metabolism; D013375:Substance Withdrawal Syndrome / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology
C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid