In the primary pathway of alcohol metabolism, alcohol is initially converted to acetaldehyde by alcohol dehydrogenase, and then to acetate by aldehyde dehydrogenase. The ALDH2 (rs671) gene codes for the primary liver isoenzyme involved in conversion of acetaldhyde to acetate. ALDH2 has two allelic forms, the wild type ALDH2*1 (ALDH2*Glu487) and the variant ALDH2*2 (ALDH2*Lys487). ALDH2*2 is extremely rare in non-Asians, but present in about 30-50% of northeastern Asians (Chinese, Koreans, Japanese) with a small percentage (about 5%) homozygous for this allele (Goedde et al., 1992). ALDH2*2 has been consistently and strongly associated with decreased rates of alcohol problems and AUDs. In a meta-analysis, having one ALDH2*2 allele was associated with a four-to-five-fold reduction in alcohol dependence (odds ratio, OR = 0.22) and having two ALDH2*2 alleles was associated with an eight-to-nine-fold reduction in alcohol dependence (OR = 0.12; Luczak et al., 2006).
