Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

Alcohol Intolerance [T51.9]

OMIM numbers: 610251, 100650 (ALDH2), 103720 (ADH2)

Dipl.-Biol. Birgit Busse

Scientific Background

Alcohol intolerance is characterized by acute signs such as flushing, tachycardia or muscle weakness after the consumption of little amounts of alcohol. Alcohol intolerance is caused by an increased concentration of the alcohol metabolite acetaldehyde in the body. This increase in concentration may be due to a change in the activity of the enzymes involved in the degradation of alcohol. The amino acid substitution Arg47His in the alcohol dehydrogenase type-2 gene (ADH2) leads to an enzyme with considerably increased activity, which causes the alcohol to be broken down into acetaldehyde to a higher degree and the metabolite to accumulate in the body. The amino acid substitution Glu487Lys in the acetaldehyde dehydrogenase type-2 gene (ALDH2) also causes an increased accumulation of acetaldehyde, since the variant enzyme shows no activity any longer and acetaldehyde therefore can no longer be degraded by this pathway.

The genetically-caused alcohol intolerance predominantly occurs within the Asian population groups. The variants p.R47H in the ADH2 gene (ADH2*2 allele) and p.E487K in the ALDH2 gene (ALDH2*2 allele) are associated with an elevated sensitivity to alcohol and are part of the routine diagnostics.