| Project/Area Number |
03454203
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
公衆衛生学
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| Research Institution | University of Tsukuba |
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Principal Investigator |
HARADA Shoji University of Tsukuba Institute of Community Medicine Associate Professor, 社会医学系, 助教授 (60086618)
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| Co-Investigator(Kenkyū-buntansha) |
SATO Shinji University of Tsukuba Institute of Community Medicine Lecturer, 社会医学系, 講師 (90162437)
TANAKA Einosuke University of Tsukuba Institute of Community Medicine Lecturer, 社会医学系, 講師 (30138416)
SHIMOJO Nobuhiro University of Tsukuba Institute of Community Medicine Professor, 社会医学系, 教授 (00080622)
ODA Susumu University of Tsukuba Institute of Community Medicine Professor, 社会医学系, 教授 (90049156)
MISAWA Shogo University of Tsukuba Institute of Community Medicine Professor, 社会医学系, 教授 (50086534)
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| Project Period (FY) |
1991 – 1993
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| Project Status |
Completed (Fiscal Year 1993)
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| Budget Amount *help |
¥5,300,000 (Direct Cost: ¥5,300,000)
Fiscal Year 1993: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1992: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1991: ¥3,100,000 (Direct Cost: ¥3,100,000)
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| Keywords | GABA / GABA autoreceptor / GABA-Transaminase / ALA / ALA-Dehydratase / Gs protein / Alcoholism / genetic polymorphism / autoreceptor / ALA-dehydratase / 遺伝子型 / GSSG / 酵素活性阻害 / GABA受容体 / 幻覚 / ALA dehydratase / ALAD1型 / アルコール依存症 / GABAーTransaminase / アルコ-ル離脱症状 / Gs蛋白 / Adenyl Cyclase / 赤血球膜 / GABAT多型 / アルコ-ル依存症 |
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| Research Abstract |
This study aimed investigation of genetic backgrounds for the symptoms such as siezurs and hallucination in relating with alcoholism. There has been strong evidence that release of gamma-aminobutyric acid (GABA) is subject to negative feedback control through presynaptic receptors on GABAergic terminals. Therefore, we studied GABA metabolic enzyme (GABA-Transaminase) (GABAT) delta-aminobutyric acid (ALA) dehydratase (ALAD) and stimulatory GTP-binding proteins (Gs).
1) Genetic polymorphism of GABAT and ALAD were investigated from the aspect of the association with alcohol related diseases. GABAT showed three different genotypes classified 1,2-1 and 2. Gene frequencies of GABAT^<**>2 was found significantly higher in alcoholic patients (0.667) than in healthy controls (0.380) (P<0.005). Strong association was observed between GABAT genotypes and hallucination in alcoholics. The patients showed hallucination positive symptom had mostly 2 or 2-1 genotype. In addition, homozygote of ALAD^<**>1 allele detected by Mps-RFLP showed a good correlation to alcoholism. Thus, the genetic polymorphism of GABAT and ALAD can be applied widely for the study of genetic association with alcoholic diseases.
2) Activity of stimulatory GTP-binding regulatory proteins (Gs) in human erythrocyte membranes was assessed by activation of adenylyte cyclase in S49 murine lymphoma variant cells to elucidate a relationship to alcohol consumption. In apparently healthy subjects, alcohol consumption < 50g ethanol per week did not alter the Gs activity, but it was significantly higher (14.3%, P0.05) in moderate drinkers (50-150g/week) than non-drinkers. Then, the Gs activity declined with a further increase in alcohol consumption (150-550g/week). The results indicate that the Gs activity in erythrocyte membranes is an alcohol-related marker in humans.
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