Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill

Center Line 
            Volume 8, No. 1, 1996 
            Director's Column
            Dr. Fulton T. Crews, Director
            
            
            
    Studies on the genetics of alcoholism offer the great hope that 
            focused prevention and treatment might substantially reduce the 
            development of alcoholism and improve the success of treatment. 
            There is no doubt that genetics are involved. I know several 
            recovered alcoholics who laughingly state they can't understand how 
            anyone can have two glasses of wine at dinner and that's all. 
            Alcoholics know they respond differently to alcohol. However, people 
            are different and alcoholism is not homogeneous. Like cancer and 
            hypertension, a combination of genetics and environment clearly 
            interplay as the disease develops. If we know who is at risk, 
            increased screening and early and aggressive intervention may 
            significantly increase prevention. Currently, early screens are not 
            used and initial interventions are minor - more like the treatment 
            of hypertension than cancer. 
            Attributing cause to genetics and genes is tricky. J.C. Garbutt's 
            studies on metabolism suggest liver genes, but sweet preference is 
            likely in the brain or sweet taste buds of the tongue (see cover 
            story this Center Line). Some of the best current evidence that 
            genetics is involved in alcoholism concerns genes expressed 
            predominantly in the liver. People with a variant aldehyde 
            dehydrogenase, an enzyme that breaks down the main metabolite of 
            ethanol-acetaldehyde, have increased levels of acetaldehyde. This 
            causes intense flushing, nausea and other unpleasant symptoms. This 
            genetic Antibuse is expressed predominantly in a small group of 
            Asians and results in a much lower incidence of alcoholism in those 
            individuals having this variant. The differences are only apparent 
            when these individuals drink. There are 50,000 to 100,000 genes in 
            the human genome and each gene likely has a number of variants. 
            Understanding how these genes interact during the development of 
            alcoholism is one of the great challenges of modern molecular 
            medicine. 
            Folklore has suggested it for some time, but only in the past few 
            decades have studies indicated that alcoholism is partly inherited 
            and not solely caused by environmental factors. Some families I know 
            will clearly comment that they know who in their family got "it," 
            that is the genetic trait that makes people vulnerable. Genetic 
            studies have indicated that humans with a predisposition to 
            alcoholism have different brain waves, e.g. P300 evoked related 
            potentials, and decreased alcohol hormone responses, e.g. cortisol, 
            and reported subjective feelings of intoxication. Among young males, 
            a low level of response to alcohol appears to be a predictor of 
            subsequent severe alcohol problems in later years. 
            A major research effort, "The Collaborative Study on the Genetics of 
            Alcoholism" (COGA), which is funded by the National Institute on 
            Alcohol Abuse and Alcoholism, is improving diagnostic, physiological 
            and molecular approaches to understanding the genetics of this 
            complex and heterogeneous disease. These studies continue to provide 
            clues and insight into contributions of genetics to alcoholism. 
            Animals can be bred to drink quantities of alcohol significant 
            enough to cause them to mimic human alcoholics. Animal studies have 
            many advantages, including control of environment and homogeneous 
            genetic backgrounds. The brains of "alcoholic rodents" show 
            neurochemical differences consistent with human models of 
            alcoholism. But the different strains are not all the same, again 
            mimicking humans. A combination of approaches is likely to help in 
            diagnosis and treatment efforts, as well as allowing early, focused 
            and aggressive intervention where appropriate. 
            Some of our most talented citizens are affected by alcoholism, and 
            early prevention will help keep people on track. The genes for 
            alcoholism are not destiny, only risk. 
            Understanding Alcoholism - Neurosciences Day - Director's Column - 
            Contents - Other Centerlines 
    
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