Genetic and Epidemiological study on alcohol withdrawal

酒精戒断的遗传学和流行病学研究

• 批准号: 03454203
• 负责人: HARADA Shoji
• 金额: $ 3.39万
• 依托单位: University of Tsukuba
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-03454203/
• 关键词: 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

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.

本研究旨在调查与酗酒相关的症状（例如癫痫和幻觉）的遗传背景。有强有力的证据表明，γ-氨基丁酸 (GABA) 的释放受到 GABA 能末端突触前受体的负反馈控制。因此，我们研究了GABA代谢酶（GABA-转氨酶）（GABAT）δ-氨基丁酸（ALA）脱水酶（ALAD）和刺激性GTP结合蛋白（Gs）。1）从与酒精相关疾病的关联角度研究了GABAT和ALAD的遗传多态性。 GABAT 显示出三种不同的基因型，分类为 1,2-1 和 2。发现酒精患者中 GABAT^<**>2 的基因频率 (0.667) 显着高于健康对照者 (0.380) (P<0.005)。在酗酒者中观察到 GABAT 基因型与幻觉之间存在很强的关联。出现幻觉阳性症状的患者多为2或2-1基因型。此外，Mps-RFLP检测到的ALAD^<**>1等位基因纯合子与酗酒有良好的相关性。因此，GABAT和ALAD的遗传多态性可广泛应用于酒精疾病遗传关联的研究。2)通过激活S49鼠淋巴瘤变异细胞中的腺苷酸环化酶来评估人红细胞膜中刺激性GTP结合调节蛋白(Gs)的活性，以阐明其与饮酒的关系。在表面健康的受试者中，每周饮酒< 50g乙醇不会改变Gs活性，但中度饮酒者（50-150g/周）的Gs活性显着高于不饮酒者（14.3%，P0.05）。然后，随着饮酒量（150-550克/周）的进一步增加，Gs活性下降。结果表明，红细胞膜中的 Gs 活性是人类酒精相关的标志物。

项目成果

原田勝二: "日本人における胃粘膜σ-ADHアイソザイムの検索" アルコールと医生物学. 16. 57-61 (1993)

Katsuji Harada：“在日语中搜索胃粘膜 σ-ADH 同工酶”《酒精与医学生物学》16. 57-61 (1993)。

原田 勝二: "アルコ-ル依存症患者のGABAーTransaminase変異型の検索" アルコ-ル代謝と肝. 11. 20-24 (1992)

Katsuji Harada：“寻找酒精患者中的 GABA 转氨酶变异”《酒精代谢与肝脏》11. 20-24 (1992)。

原田勝二: "アルコール依存症患者のGABA-Transaminase変異型の検索" アルコール代謝と肝. 11. 20-24 (1992)

Katsuji Harada：“寻找酒精患者中的 GABA 转氨酶变异”《酒精代谢与肝脏》11. 20-24 (1992)。

原田 勝二: "日本人における胃粘膜Sigma ADH(ADH6)アイソザイムの検索" アルコール医生物学. 13. (1993)

Katsuji Harada：“在日本人中寻找胃粘膜 Sigma ADH（ADH6）同工酶”《酒精医学生物学》13。（1993）

原田 勝二: "先天性代謝疾患" アルコール代謝酵素、肝胆膵. 25. 1089-1096 (1992)

Katsuji Harada：“遗传性代谢疾病”酒精代谢酶，肝胆胰。25。1089-1096（1992）