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.
KeywordsAlcoholism NR2B receptor DNA methylation mRNA Alcohol withdrawal
- Abdolmaleky HM, Cheng KH, Faraone SV, Wilcox M, Glatt SJ, Gao F, Smith CL, Shafa R, Aeali B, Carnevale J, Pan H, Papageorgis P, Ponte JF, Sivaraman V, Tsuang MT, Thiagalingam S (2006) Hypomethylation of MB-COMT promoter is a major risk factor for schizophrenia and bipolar disorder. Hum Mol Genet 15:3132–3145PubMedCrossRefGoogle Scholar
- Bleich S, Kornhuber J (2005) Part III. Schizophrenia: glutamate and schizophrenia and the N-methyl-d-aspartate receptor hypofunction hypothesis. In: Schmidt WJ, Reith MEA (eds) Dopamine and glutamate in psychiatric disorders. Humana Press, Totowa, pp 169–179Google Scholar
- Frieling H, Bleich S, Otten J, Romer KD, Kornhuber J, de Zwaan M, Jacoby GE, Wilhelm J, Hillemacher T (2008) Epigenetic Downregulation of Atrial Natriuretic Peptide but not Vasopressin mRNA Expression in Females with Eating Disorders is Related to Impulsivity. NeuropsychopharmacologyGoogle Scholar
- Hillemacher T, Frieling H, Luber K, Yazici A, Muschler MA, Lenz B, Wilhelm J, Kornhuber J, Bleich S (2008b) Epigenetic regulation and gene expression of vasopressin and atrial natriuretic peptide in alcohol withdrawal. PsychoneuroendocrinologyGoogle Scholar
- Kim MS, Yamashita K, Baek JH, Park HL, Carvalho AL, Osada M, Hoque MO, Upadhyay S, Mori M, Moon C, Sidransky D (2006) N-methyl-d-aspartate receptor type 2B is epigenetically inactivated and exhibits tumor-suppressive activity in human esophageal cancer. Cancer Res 66:3409–3418PubMedCrossRefGoogle Scholar