Mutation of mitochondrial DNA in livers from patients with alcoholic hepatitis and nonalcoholic steatohepatitis.
BACKGROUND
In alcoholic hepatitis (Al-Hep) and nonalcoholic steatohepatitis (NASH), triglycerides accumulate in hepatocytes. We examined the hypothesis that mutations in mitochondrial DNA may take place by mitochondrial overwork, resulting in dysfunction of mitochondria.


METHODS
Subjects of this research were 8 cases each of Al-Hep, NASH, and fatty liver (FL). Total DNA was extracted from the biopsied liver samples. DNA fragments were amplified by PCR and DNA sequences determined in the control and coding regions of mitochondrion.


RESULTS
When the numbers of mutations per 1,000 bases of mitochondrial DNA were compared between each group, no significant differences were found among D-loop, HV1, and HV2 mitochondrial DNA regions. However, there were significantly more mutations in ND1 and COII of Al-Hep and NASH than in FL, and mutations were comparatively at random. Neither a region in which mutations were focused nor differences among the groups were recognized. When details of the base mutation in a control region were investigated by group, the transition type of mutation between T:A<<->>C:G occurred in at least 70%. Also, a transition-type mutation was found mostly in a coding region, which was similar to the mutation pattern in the control region, except for the ND1 and COII regions where there were hardly any mutations.


CONCLUSIONS
As gene mutations of mitochondrial DNA appeared frequently in Al-Hep, and also in NASH, mitochondrial dysfunction caused by mutation in mitochondrial DNA may be involved in the pathogenesis of both diseases.
Kawahara
Hiromu
H
Department of Gastroenterology, Kanazawa Medical University, Ishikawa, Japan. hiromu@kanazawa-med.ac.jp
Fukura
Masayuki
M
Tsuchishima
Mutsumi
M
Takase
Shujiro
S
D000328:Adult; D001706:Biopsy; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D005234:Fatty Liver / Q000235:genetics* / Q000473:pathology; D006519:Hepatitis, Alcoholic / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008099:Liver / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction
D004272:DNA, Mitochondrial