Perhaps the strongest evidence for GxE interaction effects in alcoholism etiology comes from Japanese researchers who analyzed the effects of the gene that carries the information for aldehyde dehydrogenase 2 (ALDH2), an enzyme that plays a pivotal role in alcohol metabolism in the body. Two alleles of the ALDH2 gene exist. The ALDH2–1 allele effectively converts acetaldehyde, a breakdown product of alcohol, into acetate and water. The ALDH2–2 allele, however, is inactive, resulting in the accumulation of acetaldehyde, which exerts several toxic effects (e.g., a flushing response, nausea, and increased heart rate). Because each person inherits two copies of the ALDH2 gene—one from the mother and one from the father—one can carry either two ALDH2–1 alleles (i.e., be homozygous for ALDH2–1), one ALDH2–1 and one ALDH2–2 allele (i.e., be heterozygous), or two ALDH2–2 alleles (i.e., be homozygous for ALDH2–2). People who are heterozygous experience a flushing response after consuming alcohol and have a substantially reduced risk of alcohol dependence compared with people who are homozygous for the functional ALDH2–1 allele. People who are homozygous for the defective ALDH2–2 allele experience
