Genetic and Epidemiological study on alcohol withdrawal

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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.