Studies on the dominant negative effect of the ALDH2*2 allele.

Abstract

The alcohol flush reaction results from a dominantly inherited deficiency in the activity of mitochondrial aldehyde dehydrogenase (ALDH2) (Harada et al., 1982; Goedde et al, 1989). The active and inactive alleles are named ALDH2*1 and ALDH2*2, respectively. Consumption of alcohol by individuals with the deficiency leads to dramatic increases in blood acetaldehyde levels. The aversive symptoms that they experience from this acetaldehyde accumulation reduces their consumption of alcohol and greatly reduces the risk that they will become alcoholics (Goedde et al., 1983; Harada et al., 1983; Thomasson et al., 1991). In fact, it is the most powerful genetic modifier of alcohol consumption yet discovered. This protection may be a two-edged sword; several recent studies have shown increased frequency of ALDH2*2 heterozygotes among alcoholics with cirrhosis compared with alcoholics without evidence of liver disease (Chao et al., 1994; Yamauchi et al., 1995; Tanaka et al., 1996), although in both groups the frequency of heterozygotes is lower than in the non-alcoholic control population.KeywordsAldehyde DehydrogenaseDominant Negative EffectALDH2 ActivityAlcoholic Liver CirrhosisAldehyde Dehydrogenase GeneThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.