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Researchers find new genetic influences on alcohol metabolism

"We have known for a long time that individuals from East Asia often have a variant form of ALDH that works slowly to eliminate alcohol," said Crabbe, "and these individuals experience the bad side effects when they drink. As you can imagine, very few Asians with the variant ALDH become alcoholics. Because we inherit which form of ALDH we have from our parents, this is a very clear example of a gene that is protective against alcoholism."

Scientists have used this genetic knowledge to create at least one form of treatment for alcoholism, said Richard Deitrich, professor of pharmacology at the University of Colorado School of Medicine. "The drug Antabuse or disulfiram is used in alcoholics to inhibit aldehyde dehydrogenase, thereby achieving elevated levels of acetaldehyde, and thus deter these individuals from drinking," he said. "In short, about half of all Asians have a genetic deterrent to drinking, while Occidentals have to do it through chemistry."

Still, which variants of alcohol dehydrogenase or ALDH an individual has cannot explain all of the different rates of alcohol metabolism. Using mouse models - the genomes of mice and humans are likely more than 80% similar - researchers searched for additional genes of importance. They focused on two inbred mouse strains that have been used extensively to identify genes influencing traits associated with drug abuse and alcoholism. One was B6, known to prefer alcohol solutions to water, and the other was D2, known to avoid alcohol; additionally, they looked at 25 BXD RI strains, each of which is a cross between B6 and D2 mice. Following alcohol injections (of either 2 or 3 g/kg alcohol), blood alcohol concentrations and alcohol metabolism rates were measured in all 27 strains at several time points and then correlated with polymorphic markers.

"One interesting aspect of this paper is that they did not find any genetic 'hot spots' for either alcohol or aldehyde dehydrogenases," said
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15-May-2002


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