DNA hypermethylation of the alpha synuclein promoter in patients with alcoholism

Abstract

The aim of this study was to investigate whether the DNA methylation pattern within the alpha synuclein promoter region is altered in intoxicated and early abstinence patients with alcoholism undergoing alcohol withdrawal. We observed a significant increase of the alpha synuclein promoter DNA methylation in patients with alcoholism which was significantly associated with their elevated homocysteine levels. No significant differences of the promoter DNA methylation within a control gene (presenilin-1) in alcoholics and controls were found. The present results hint to a gene specific DNA promoter hypermethylation within the alpha synuclein gene. Since hypermethylation of DNA is an important epigenetic factor in the down regulation of gene expression and since alpha synuclein has been linked to craving these findings may explain the reduced value of craving under alcohol drinking conditions.

Prospects for Epigenetic Epidemiology

“…Human case-control studies have demonstrated that alcohol consumption increases methylation at gene promoters (108)(109)(110)(111) and is associated with methylation-induced silencing of tumor suppressor genes in colorectal cancer (112) and hyperhomocysteinemia (113). Alcohol consumption is also associated with altered levels of methyltransferase activity and DNA methylation (71,109).…”

Global DNA hypomethylation and DNA hypermethylation of the alpha synuclein promoter in females with anorexia nervosa

“…Analysis of global and gene-specific DNA methylation and expression of the two genes investigated was performed as was recently described by us. 5,7 Betweengroup comparisons were performed by t-tests or one-way analysis of variance (ANOVA), followed by all pairwise comparisons according to Bonferroni using SPSS for Windows 14.0 (SPSS Inc., Chicago, IL, USA).…”

Neurogenetic studies of alcohol addiction

“…Increased plasma homocysteine levels were also correlated with cognitive deficits in early withdrawal (Wilhelm et al 2006). The DNA hypermethylation is pronounced in the area of the alpha synuclein, but not the presenilin 1, promoter (Bonsch et al 2005b). Thus, the alpha synuclein story may depend upon epigenetic modifications of the expression of other genes as yet unidentified.…”