Think of a person's genetic makeup as a gigantic orchestra. Each of the instruments' notes represents a gene, a protein. Various cell types can combine notes and chords into simple or complex variations. Sometimes the music flows seamlessly, sometimes a wayward note can destroy a certain passage, even the entire concert. Gene mutations are like discordant musical notes. Just as mutation of the hemoglobin gene can cause sickle-cell anemia, so too can genetic mutation of the liver enzyme aldehyde dehydrogenase (ALDH) cause a person to have an aversive reaction to alcohol.
"The major way you eliminate alcohol is via the liver," said Matt McGue, professor and chair of the Department of Psychology at the University of Minnesota. "There are two enzymes that regulate the metabolism of alcohol. First, alcohol dehydrogenase (ADH) converts alcohol into acetaldehyde. Second, ALDH converts acetaldehyde to acetate." Acetate is then metabolized by tissues outside of the liver.
"Acetaldehyde is a toxic compound," said Ting-Kai Li, Distinguished Professor at the Indiana
University School of Medicine and one of the study's authors, "and the body has an aversive reaction
to it." This aversion can manifest itself through cardiovascular complications, hypothermia, nausea,
asthma and facial flushing. "If the ALDH enzyme is normal then the acetaldehyde is metabolized very
quickly and people don't have this reaction," said Li. "If there is a genetic mutation of that
enzyme, it becomes very inefficient and cannot metabolize
Contact: Ting-Kai Li, M.D.
Alcoholism: Clinical & Experimental Research