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

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• 作者：Teresa Biermann ; Udo Reulbach ; Bernd Lenz ; Helge Frieling ; Marc Muschler ; Thomas Hillemacher ; Johannes Kornhuber and Stefan Bleich
• 关键词：Alcoholism ; NR2B receptor ; DNA methylation ; mRNA ; Alcohol withdrawal
• 刊名：Journal of Neural Transmission
• 出版年：2009
• 出版时间：May, 2009
• 年：2009
• 卷：116
• 期：5
• 页码：615-622
• 全文大小：291.5 KB

文摘

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.