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

J Neural Transm (Vienna). 2006 Sep;113(9):1299-304. doi: 10.1007/s00702-005-0413-2. Epub 2006 Feb 6.

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.

MeSH terms

  • Adult
  • Aged
  • Alcoholism / enzymology*
  • Alcoholism / genetics*
  • Central Nervous System Depressants / blood
  • DNA (Cytosine-5-)-Methyltransferases / biosynthesis*
  • DNA (Cytosine-5-)-Methyltransferases / genetics
  • DNA Methylation*
  • DNA Methyltransferase 3A
  • DNA Methyltransferase 3B
  • Ethanol / blood
  • Homocysteine / blood
  • Humans
  • Isoenzymes / biosynthesis
  • Isoenzymes / genetics
  • Male
  • Middle Aged
  • Psychiatric Status Rating Scales
  • RNA, Messenger / biosynthesis*
  • RNA, Messenger / genetics
  • Socioeconomic Factors

Substances

  • Central Nervous System Depressants
  • DNMT3A protein, human
  • Isoenzymes
  • RNA, Messenger
  • Homocysteine
  • Ethanol
  • DNA (Cytosine-5-)-Methyltransferases
  • DNA Methyltransferase 3A