Hepatic mitochondrial DNA deletion in alcoholics: association with microvesicular steatosis.
OBJECTIVE
Alcohol abuse may lead to microvesicular steatosis, a lesion ascribed to impaired mitochondrial function. Because alcohol abuse leads to reactive oxygen species in the hepatic mitochondria, it may damage mitochondrial DNA. The aim of this study was to look for the presence of the "common" 4977-base pair deletion in the hepatic mitochondrial DNA of alcoholic patients and age-matched, nonalcoholic controls.


METHODS
Hepatic DNA was subjected to two polymerase chain reactions that amplified non-deleted and deleted mitochondrial DNA, respectively.


RESULTS
The deletion was found in 6 of 10 alcoholics with microvesicular steatosis, 2 of 17 alcoholic patients with macrovacuolar steatosis, but in none of 12 patients with acute alcoholic hepatitis, 11 patients with alcoholic cirrhosis, or 62 nonalcoholic patients of comparable ages with various other liver diseases or normal liver histology. In all patients with the deletion, restriction fragments of deleted mitochondrial DNA co-migrated with those of reference Pearson bone marrow-pancreas syndrome patients with the common mitochondrial DNA deletion.


CONCLUSIONS
The common deletion is frequent in the hepatic DNA of alcoholic patients with microvesicular steatosis. Alcohol-induced mitochondrial DNA damage may contribute to the occurrence of this lesion in some alcoholics.
Fromenty
B
B
INSERM Unité 24, Hôpital Beaujon, Clichy, France.
Grimbert
S
S
Mansouri
A
A
Beaugrand
M
M
Erlinger
S
S
Rötig
A
A
Pessayre
D
D
D000328:Adult; D000437:Alcoholism / Q000150:complications* / Q000235:genetics*; D001483:Base Sequence; D004272:DNA, Mitochondrial / Q000235:genetics* / Q000378:metabolism; D005234:Fatty Liver / Q000150:complications*; D005260:Female; D017353:Gene Deletion; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008102:Liver Circulation; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D012016:Reference Values
D004272:DNA, Mitochondrial; D015335:Molecular Probes