Alcoholism is a complex disorder that arises from both genetic factors and environmental influences. According to the National Institute on Alcohol Abuse and Alcoholism, a person's genes account for about 50 to 60 percent of the risk of becoming an alcoholic. The risk comes from many genes, each with a small effect, acting together to determine the overall response of the body to alcohol. Scientists have discovered only a few genes that have a fairly strong effect on the risk of alcoholism.
ADH
A mutation in the gene called ADH can protect people from alcoholism. The gene ADH on chromosome 4 encodes the liver enzyme alcohol dehydrogenase, which speeds up the first step of alcohol metabolism, the conversion of alcohol to acetylaldehyde. When this first step occurs too quickly, acetylaldehyde levels build up causing facial flushing, nausea and a racing heart in response to small amounts of alcohol.
As reviewed by Dr. Sarah Hartz and Dr. Laura Beirut in the March 2010 issue of "Psychiatric Clinics of North America," many people of Asian descent inherit a mutant form of the ADH gene called ADH1B*2. This form of the gene encodes a hyper-efficient enzyme that rapidly converts alcohol to acetylaldehyde, causing acetylaldehyde levels to build up. People with one copy of ADH1B*2 are 10 times less likely to become alcoholics than other people, presumably because even one drink has such unpleasant consequences. ADH1B*2 is common in people of Asian descent but uncommon in people of African or European descent, and the protective effect is not as strong in Europeans as in Asians.
ALDH2
A mutation in a gene on the long arm of chromosome 12 called ALDH2 can also protect against alcoholism. In the second step of alcohol metabolism, ALDH2 turns acetylaldehyde into acetate. When ALDH2 does not work properly, acetylaldehyde levels build up. Dr. Hartz and Dr. Beirut cite a study showing that many people of Asian descent have a deficiency in ALDH2. One study that they cited found that 41 percent of the general population of Japanese lacked ALDH2 enzyme, while only 2 percent of Japanese alcoholics lacked the enzyme. Later studies found that a specific form of the gene called ALDH2*2 makes a faulty enzyme that cannot properly metabolize alcohol. People with one copy of ALDH2*2 have one-third of the normal risk of becoming alcoholics; alcoholics with two copies of ALDH2*2 are so rare that their description merits a paper in a scientific journal. ALDH2*2 is common in people of Asian descent but very uncommon in people of African or European descent.
GABA Receptors
Alcohol disrupts coordination, lowers inhibitions, and relieves anxiety by stimulating receptors for a nerve chemical called GABA. The gene GABRA2 encodes a sub-unit of the GABA receptor. As Dr. Hartz and Dr. Beirut discuss, certain forms of the GABRA2 gene are associated with an increased risk for alcoholism, presumably because they heighten the pleasant effects of alcohol. GABA receptors also contribute to the symptoms of alcohol withdrawal, so people with certain forms of GABRA2 might find it more difficult to quit drinking.
References
- National Institute on Alcohol Abuse and Alcoholism: Alcohol Alert
- "Psychiatric Clinics of North America"; Sarah Hartz and Laura Beirut; Genetics of Addiction; March 2010.
