Lowered DNA methyltransferase (DNMT-3b) mRNA expression is associated with genomic DNA hypermethylation in patients with chronic alcoholism

Abstract

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.

Alcohol abuse and cigarette smoking are associated with global DNA hypermethylation: Results from the German Investigation on Neurobiology in Alcoholism (GINA)

“…Direct inhibition of DNA methyltransferases by alcohol has previously been described as a potential mechanism of DNA hypermethylation in alcohol dependence, which could also be the case in our patient sample (Bonsch et al, 2006;Varela-Rey et al, 2013).…”

Substance use and misuse in the aftermath of terrorism. A Bayesian meta‐analysis

“…Epigenetics will play an increasingly important role in this endeavor [61,62]. Understanding the population health effects of stressors such as fear of terrorism can help to inform such basic research.…”

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).…”

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