Genetic and Epidemiological study on alcohol withdrawal

这项研究的目的是调查与酒精中毒有关的症状的遗传背景，如酒精症和幻觉。有强有力的证据表明，γ-氨基丁酸(GABA)的释放受GABA能终末上的突触前受体负反馈控制。为此，我们对GABA代谢酶(GABA-转氨酶)(GABAT)、β-氨基丁酸(ALA)脱水酶(ALAD)和刺激性GTP结合蛋白(Gs)进行了研究。1)从与酒精相关疾病的角度研究了GABAT和ALAD的遗传多态性。GABAT有3种不同的基因类型，分别为1、2-1和2。酒精组GABAT^&lt；**&gt；2基因频率(0.667)显著高于正常对照组(0.380)(P&lt；0.005)。在酗酒者中观察到GABAT基因与幻觉之间有很强的相关性。幻觉阳性症状患者多为2或2-1等位基因。MPS-RFLP检测到ALAD^&lt；**&gt；1等位基因纯合子与酒精中毒有较好的相关性。因此，Gabat和ALAD的遗传多态性可广泛应用于酒精性疾病的遗传关联研究。2)通过激活S49小鼠淋巴瘤变异细胞中的腺苷环化酶来评估人红细胞膜上刺激性GTP结合调节蛋白(Gs)的活性，以阐明其与饮酒的关系。在看似健康的受试者中，每周饮用50g酒精不会改变Gs活性，但中度饮酒者(50-150g/周)的Gs活性显著高于不饮酒者(14.3%，P<0.05)。然后，Gs活性随着饮酒量的进一步增加而下降(150-550g/周)。结果表明，红细胞膜Gs活性是人类与酒精有关的标志物。

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.