To our knowledge, this is the first study evaluating HERP mRNA expression and its specific gene promoter methylation in alcoholic patients. As hypermethylation of DNA is an important epigenetic factor in the down-regulation of gene expression, and as HERP has been considered to play an essential role within the intracellular defense system, these findings may be useful in the understanding and treatment of different disease conditions associated with alcohol dependence.

Higher plasma homocysteine concentrations can influence genomic DNA methylation in peripheral blood cells. In the present controlled study we observed a significant increase (10%) of genomic DNA methylation in patients with alcoholism (t = -3.16, df = 158, p = 0.002) which was significantly associated with their elevated homocysteine levels (multiple linear regression, p < 0.001). Since methylation of DNA is an important epigenetic factor in regulation of gene expression these findings may have important implications for a possible subsequent derangement of epigenetic control these patients.

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.

DNA methyltransferases (DNMTs) are involved within the epigenetic control of DNA methylation processes. Recently, it has been shown that the genomic DNA methylation in patients with alcoholism is increased. In the present controlled study we observed a significant decrease of mRNA expression of DNMT-3a and DNMT-3b when comparing alcoholic patients (n = 59) with healthy controls (n = 66): DNMT-3a (t = -2.38, p = 0.019), DNMT-3b (t = -2.65, p = 0.008). No significant differences were seen for DNMT-1 and Mbd-2 (Methyl-CpG-Binding-Domain protein 2) expression. Additionally, we observed a significant negative correlation between DNMT-3b expression and the blood alcohol concentration (r = -0.45, p = 0.003) which might explain the decrease of DNMT-3b mRNA expression in alcoholic patients. Using a multivariate model we observed that the increase (10%) of genomic DNA methylation in patients with alcoholism was significantly associated with their lowered DNMT-3b mRNA expression (multiple linear regression, p = 0.014). Since methylation of DNA is an important epigenetic factor in regulation of gene expression these findings may have important implications for a possible subsequent derangement of epigenetic control in these patients.