Ethanol metabolism, toxicity and genetic polymorphism

Abstract The relationships between the individual (and racial) differences in alcohol metabolism and toxicity, and the genetic polymorphism of alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), and cytochrome P‐4502E1(CYPIIE1) were reviewed. In recent studies involving DNA analysis, it was found that a deficiency of the ALDH2 isozyme (ALDH2*2) was responsible for the flushing symptoms as well as other vasomotor symptoms caused by a higher acetaldehyde level after alcohol consumption. Deficiency of ALDH2 activity has been found prevalently only among people of Mongoloid origin, and the deficiency of ALDH2 prevents them from developing alcohol dependence due to the unpleasant physical effects of the flushing symptom. It was reported that Mongoloids such as Japanese and Chinese people carry the enzymatically active (ALDH2*1) subunit and/or the inactive (ALDH2*2) one, and that a low proportion of ALDH2 deficiency (ALDH2*2 allele frequency) was found in alcoholics compared with healthy controls. It was also reported that polymorphism of ALDH2 and/or CYP2E1 may be associated with the susceptibility to alcohol‐induced liver injury. Concerning blood ethanol elimination kinetics, it was reported that the c2 gene of CYP2E1 and the ALDH2*1 gene may have greater effects on ethanol and acetaldehyde elimination than the other genotypes, when the blood ethanol level is below 20 m M.