| Project/Area Number |
02670257
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Legal medicine
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| Research Institution | Shiga University of Medical Science |
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Principal Investigator |
YAMADA Mitsuko Shiga University of Medical Science Department of Legal Medicine Research Associate, 医学部, 助手 (80145911)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAMOTO Yoshio Shiga University of Medical Science Department of Legal Medicine Research Associ, 医学部, 助手 (60111902)
FUKUNAGA Tatsushige Shiga University of Medical Science Department of Legal Medicine Associate Profe, 医学部, 助教授 (70156800)
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| Project Period (FY) |
1990 – 1991
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| Project Status |
Completed (Fiscal Year 1991)
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| Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1991: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1990: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | Ethanol metabolism / Alcohol dehydrogenase / Aldehyde dehydrogenase / DNA analysis |
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| Research Abstract |
In an individual ethanol sensitivity, allelic differences at the alcohol and aldehyde dehydrogenases (ADH, ALDH) loci may have an important role. We distinguished the polymorphism at the ADH2 and ALDH2 loci in Japanese individuals'white cell DNAs using allele-specific oligonucleotide probes directed at their single base pair differences. The activity of the ALDH2 isozyme in their hair roots was also detected. The individuals were orally administered 0.4 g/kg of ethanol and their flushing symptom and the blood ethanol and acetaldehyde concentrations were determined.
Frequencies of ADH2^*1/ADH2^*1, ADH2^*1/ADH2^*2 and ADH2^*2/ADH2^*2 in the healthy Japanese were 11, 49 and 40 %, respectively and those of ALDH2^*1/ALDH2^*1, ALDH2^*1/ALDH2^*2 and ALDH2^*2/ALDH2^*2 were 48, 44 and 8 %, respectively. The homozygous genotype of ALDH2^*1 showed an enzymatically active ALDH2 band and the isozymes containing the subunit of ALDH2^*2 had no activity and caused the facial flushing. The heterozygotes had been evaluated as the 'ALDH2 deficient' individuals in the previous studies analyzing the ALDH2 isozyme in hair root samples. The homozygous genotype of ALDH2^*2 showed the highest acetaldehyde concentrations after alcohol intake, while the subjects showing heterozygous genotype had higher concentrations than those of homozygous genotype of ALDH2^*1. The beta_<60> values for ethanol and the ethanol elimination rates were higher in the ALDH2 normal homozygote than in the heterozygote and the mutant homozygote. These facts were observed in any ADH2 genotypes.
In the subject possessing ALDH2^*2 allele a consequent elevation of blood acetaldehyde after alcohol intake due to less or no enzyme activity causes strong sensitivity to ethanol and seems to play an inhibitory role in the first step of ethanol metabolism. ADH polymorphisms make no differences in the ethanol metabolism or sensitivity.
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