Most Caucasians have two major isozymes, while approximately 50% of East Asians have one normal copy of the ALDH2 gene and one variant copy (ALDH2*2, rs671) that encodes an inactive mitochondrial isoenzyme. In native Japanese, this variant ALDH2 allele encodes lysine instead of glutamic acid at amino acid 487 and therefore encodes a product protein that is completely inactive in metabolizing acetaldehyde to acetic acid. In the overall Japanese population, about 57% of individuals are homozygous for the normal allele, 40% are heterozygous for the variant allele, and 3% are homozygous for the variant allele. Since ALDH2 assembles and functions as a tetramer and requires all four of its components to be active in order to metabolize acetaldehyde, heterozygotes have very little ALDH2 activity. Accordingly, individuals heterozygous or homozygous for the abnormal allele metabolize ethanol to acetaldehyde normally but metabolize acetaldehyde poorly and are thereby susceptible to certain adverse effects of alcoholic (i.e., ethanol-containing) beverages; these effects include the transient accumulation of acetaldehyde in blood and tissues; facial flushing (i.e. the "Asian flushing syndrome"), urticaria, systemic dermatitis, and alcohol-induced respiratory reactions such as rhinitis and the exacerbation of asthma bronchoconstriction. The cited allergic reaction-like symptoms: a) do not appear due to classical IgE or T cell-related allergen-induced reactions but rather the actions of acetaldehyde in stimulating the release of histamine, a probable mediating cause of these symptoms; b) typically occur within 30–60 minutes of ingesting alcoholic beverages; and c) occur in other Asian as well as non-Asian individuals that are either seriously defective in metabolizing ingested ethanol past acetaldehyde to acetic acid or, alternatively, that metabolize ethanol too rapidly for ALDH2 processing.