Lowered DNA methyltransferase (DNMT-3b) mRNA expression is associated with genomic DNA hypermethylation in patients with chronic alcoholism.
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.
Bönsch
D
D
Department of Psychiatry and Psychotherapy, Friedrich-Alexander-University of Erlangen-Nuremberg, Germany. dominikus.boensch@psych.imed.uni-erlangen.de
Lenz
B
B
Fiszer
R
R
Frieling
H
H
Kornhuber
J
J
Bleich
S
S
D000328:Adult; D000368:Aged; D000437:Alcoholism / Q000201:enzymology* / Q000235:genetics*; D002492:Central Nervous System Depressants / Q000097:blood; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000096:biosynthesis* / Q000235:genetics; D019175:DNA Methylation; D000090205:DNA Methyltransferase 3A; D000431:Ethanol / Q000097:blood; D006710:Homocysteine / Q000097:blood; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D012959:Socioeconomic Factors; D000097584:DNA Methyltransferase 3B
D002492:Central Nervous System Depressants; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; D000431:Ethanol; D006710:Homocysteine; D007527:Isoenzymes; D012333:RNA, Messenger; D000097584:DNA Methyltransferase 3B; C000717967:DNMT3A protein, human