The initial studies about the role of alcohol metabolism genes in alcohol sensitivity explained, at first, some of the population differences in alcohol intoxication symptoms (e.g., facial flushing, elevation of skin temperature, increase in pulse rate, and ventilation): many Asian-ancestry subjects showed an increased sensitivity to alcohol drinking compared to European-ancestry individuals [Wolff 1972]. Population screenings determined that Asian populations present higher frequencies of a highly-active hepatic ADH isoform and a highly-inactive hepatic ALDH isoform than those observed in European populations [Goedde and others 1979; Stamatoyannopoulos and others 1975]. As noted above, ADH and ALDH enzymes catalyze different steps in the process of alcohol degradation. The intermediate product of this two-step reaction is acetaldehyde, which is more toxic than ethanol itself (while more reinforcing in the CNS) and it is mainly responsible for alcohol intoxication symptoms [Brooks and Zakhari 2014]. Since both highly-active ADHs and highly-inactive ALDHs have the potential to cause increased circulating acetaldehyde levels, several authors hypothesized their possible involvement in population differences in alcohol sensitivity [Goedde and others 1979; Stamatoyannopoulos and others 1975]. These variant ADH and
