Study of mitochondrial DNA deletion in alcoholic liver disease
Project/Area Number |
08670633
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Gastroenterology
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Research Institution | Kanazawa Medical University |
Principal Investigator |
UESHIMA Yasuhiro Kanazawa Medical University, Assistant, 医学部, 助手 (20184921)
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Project Period (FY) |
1996 – 1997
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Project Status |
Completed (Fiscal Year 1997)
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Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1997: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1996: ¥1,500,000 (Direct Cost: ¥1,500,000)
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Keywords | mitochondrial DNA / heteroplasmy / mutation / alcoholic liver disease / complex V / mitochondria / mitochondria DNA / ATPase / deletion |
Research Abstract |
Recently, it has been reported that mitochondrial (Mt) DNA mutation, such as nucleotide replacement or partial deletion, resulted from the production of oxygen-free radicals can be detected frequently as a form of heteroplasmy in the tissues and blood samples from patients with alcoholic liver disease (ALD). We also have reported that Mt-DNA deletion of blood cells was detected frequently in alcoholics. However, it has been unknown whether Mt-DNA deletion of blood cells in alcoholics is caused by alcohol intake per se or by ALD.In this study, we detected the deletion of Mt-DNA encoding ATPase region in blood cells and liver tissues obtained from patients with ALD and non-ALD.Blood samples were obtained from 56 patients with ALD, 35 patients with non-ALD and 106 non-alcoholic healthy subjects. Liver biopsy samples were also obtained from 11 patients with ALD and 9 patients with non-ALD.MuDNA encoded ATPase region (8343-9218) was amplified by polymerase chain reaction (PCR) using two primers : forward primer ; 5'-AACCAACACCTCTTTACAGTGA (8343-8364) and reverse primer ; 5'-TTGGTGGGTCATTATGTGTTGT (9117-9218). Electrophoresis of PCR products was performed and bands were visualized by ethidium bromide. Heteroplasmy with 491 bp deletion in addition to normal band in blood cells was observed in 67% and 74% patients with ALD and non-ALD, respectively, while no heteroplasmy was detected in non-alcoholic healthy subjects. On the other hand, heteroplasmy of hepatic Mt-DNA was observed in 67% of ALD patients who had Mt-DNA deletion of blood cells, while no heteroplasmy was detected in non-ALD.There was no heteroplasmy of hepatic Mt-DNA in both ALD and non-ALD patients who had normal Mt-DNA of blood cells. These results suggest that Mt-DNA deletion of blood cells may not reflect liver disease including ALD and hepatic Mt-DNA deletion in ALD may be prone to be damaged by acetaldehyde and free radical.
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Report
(3 results)
Research Products
(2 results)