The effect of chronic alcohol consumption on mitochondrial DNA mutagenesis in human blood.
The 4977bp deletion of mitochondrial DNA (mtDNA) is known to accumulate with increasing age in post mitotic tissues. Recently, studies came out detecting this specific alteration also in fast replicating cells, e.g. in blood or skin tissue, often in correlation to specific diseases or -- specifically in skin -- external stressors such as UV radiation. In this study, we investigated mitochondrial mutagenesis in 69 patients with a chronic alcoholic disease and 46 age matched controls with a moderate drinking behavior. Two different fragments, specific for total and for deleted mtDNA (dmtDNA) were amplified in a duplex-PCR. A subsequent fragment analysis was performed and for relative quantification, the quotient of the peak areas of amplification products specific for deleted and total mtDNA was determined. Additionally, a real time PCR was performed to quantify mtDNA copy number. The relative amount of 4977bp deleted mtDNA in alcoholics was significantly increased compared to controls. On the other hand, no difference regarding the mtDNA/nuclear DNA ratio in both investigated groups was detected. Additionally, no age dependence could be found nor in alcoholics, neither in the control group. These findings indicate that mtDNA mutagenesis in blood can be influenced by stressors such as alcohol. Ethanol seems to be a significant factor to alter mitochondrial DNA in blood and might be an additional contributor for the cellular aging process.
von Wurmb-Schwark
N
N
Institute of Legal Medicine, Christian Albrecht University of Kiel, Arnold-Heller-Str 12, 24105, Kiel, Germany. nvonwurmb@rechtsmedizin.uni-kiel.de
Ringleb
A
A
Schwark
T
T
Broese
T
T
Weirich
S
S
Schlaefke
D
D
Wegener
R
R
Oehmichen
M
M
D000328:Adult; D000367:Age Factors; D000428:Alcohol Drinking / Q000097:blood / Q000235:genetics; D000437:Alcoholism / Q000097:blood* / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000097:blood*; D018628:Gene Dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D016296:Mutagenesis; D016133:Polymerase Chain Reaction; D017384:Sequence Deletion
D004272:DNA, Mitochondrial