Genetic aspects and risk factors in alcoholism and alcoholic liver disease.

There is a great deal of evidence for genetic predisposition to alcoholism; considerably less is known regarding predisposition to alcoholic liver disease. The specific genes involved in either disorder are not well understood, although the enzymes of alcohol metabolism appear to play some role. It will be interesting to determine whether genetic factors that alter the expression of these enzymes, in addition to altering the kinetics of the enzymes, could modify responses to drinking. Work in the next few years will include determination of which responses to alcohol are indeed genetically influenced in twin studies, testing additional candidate genes for alcohol-related traits in populations and families, as well as the application of genomic mapping methodologies to alcoholic pedigrees. The latter strategy will be integrated into the larger number of studies that will grow from the Human Genome Project. Animal studies with selectively bred lines of rodents that differ in voluntary alcohol consumption will lead the way to define the neuronal and behavioral substrates responsible for differences in alcohol-drinking behavior. The use of the quantitative trait locus (QTL) mapping approach in F2 intercross between two inbred strains of rodents with opposite alcohol-response characteristics and in recombinant inbred strains derived from F2 intercross already has and will continue to help identify chromosomal locations of genes relevant to voluntary alcohol consumption. Perhaps in the future selective breeding of rodents and QTL mapping strategies can also be used to determine the biology and genetics of alcohol-induced liver injury.