The onset of the genomics era has initiated a rapid increase in researchers’ ability to find and analyze polymorphisms within the enzymes responsible for ethanol metabolism. In fact, the rate of discovery of polymorphisms in and near these genes far outpaces the ability to functionally characterize them. Future studies of the expression and kinetic properties of the variant enzymes are important. In particular, methodologies for rapidly and accurately determining protein expression levels of specific forms are needed. For example, a commonly used approach to identify individual problems—that is, the use of specific antibodies—has not yet worked with the ADH1A, ADH1B, and ADH1C proteins because these proteins are highly conserved, with their sequence at the protein level more than 93 percent identical; moreover, many of the sequence changes are located within functional sites and not optimally situated for antibody recognition. Knowledge of expression level changes, however, will be critical to develop models for predicting the metabolic consequences of both the currently characterized functional polymorphisms and those that are yet to be discovered.
