introduction
Some people experience an unpleasant reaction to drinking even a slight amount of alcohol. Their face turns red, and sometimes they also have signs of drowsiness, increased heart rate, nausea, and symptoms of reduced blood pressure. This reaction to alcohol is called alcohol flush reaction and is most commonly seen in individuals of East Asian ancestry, which is why it is sometimes referred to as the "Asian Flush".Alcohol is toxic to human bodies. In people who do not experience alcohol flush reaction, alcohol is broken down (metabolized) in the liver into substances which can be either used or excreted by the body. This breakdown occurs in several steps (see figure). First the enzyme alcohol dehydrogenase (ADH) converts alcohol to acetaldehyde. Acetaldehyde is a substance even more toxic to the body than alcohol and contributes largely to the adverse effects of alcohol generally known as a "hangover". Second, acetaldehyde is broken down into the harmless acetic acid (or vinegar) by another enzyme called aldehyde dehydrogenase-2 (ALDH2). A third enzyme finally breaks the acetic acid into fat, carbon dioxide, and water. The impaired function of any of these critical enzymes disrupts alcohol metabolism, leading to varying degrees of discomfort depending on the amount of alcohol ingested and which enzyme is affected.
Alcohol flush reaction is largely due to a genetic variant that affects one of the enzymes responsible for breaking down (metabolizing) alcohol. This genetic variant is found in the ALDH2 gene and is known as the ALDH2*2 allele. The ALDH2 gene regulates the production of the enzyme aldehyde dehydrogenase 2 that has the role of transforming acetaldehyde into acetic acid. The ALDH2*2 allele is dominant. This means that even one copy of it interferes with the formation of a fully functional ALDH2 enzyme, with the result that acetaldehyde cannot be broken down and builds up in the body when drinking alcohol, leading to the symptoms described above.
The ALDH2*2 variant is common in individuals of East Asian descent (45-50%), but is extremely rare in most non-Asian populations.
The deCODEme Genetic Scan identifies the sequence variant (rs671) in the ALDH2 gene on chromosome 12 and gives an interpretation of the associated genetic risk for alcohol flush reaction. It does not at this time identify the sequence variants associated with the defective ADH enzyme in the first step of alcohol breakdown.
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The main cause for the alcohol flush reaction is the inheritance of one or two copies of the ALDH2*2 genetic variant causing an inactive ALDH2 enzyme as described earlier. This variant is most often found in individuals of Asian descent. Ethnicity is therefore the main risk factor.
Please note however that alcoholic beverages are often a complex mixture of grape, yeast, hop, barley or wheat-derived substances and preservatives. Regardless of the results of the deCODEme genetic scan, if you experience the described symptoms associated with alcohol flush reaction you could be sensitive to other substances in alcoholic beverages or you may be on a medication that interacts with alcohol in this way.
Having the genetic variant(s) predisposing individuals to alcohol intolerance also has an advantage; these individuals may be protected against developing alcoholism, at least partly due to the fact that they often choose to avoid alcoholic beverages altogether. Studies have indeed shown that people of Asian descent, as a whole, have lower rates of alcohol dependence compared with other ethnic groups. In fact, the knowledge behind the alcohol flush reaction has been utilized in therapeutics for alcoholism. Doctors sometimes prescribe alcoholics with a drug called disulfiram which essentially mirrors the ALDH2*2 effect (inhibits the ALDH2 enzyme) and hence discourages use and abuse of alcohol.
You can find out more information about alcohol flush reaction by talking to your doctor and visiting these Web sites:- National Institute on Alcohol Abuse and Alcoholism (NIAAA) article on the role of acetaldehyde in mediating the pharmacological and behavioral effects of alcohol.
- Wikipedia article on the alcohol flush reaction
scientific references
- Chen, C.C., Lu, R.B., Chen, Y.C., Wang, M.F., Chang, Y.C., Li, T.K., & Yin, S.J. (1999). Interaction between the functional polymorphisms of the alcohol-metabolism genes in protection against alcoholism. The American Journal of Human Genetics, 65(3), 795-807.
- Edenberg, H.J. (2007). The genetics of alcohol metabolism. Alcohol Research & Health, 30(1), 5-13.
- Eng, M.Y., Luczak, S.E., & Wall, T.L.(2007). ALDH2, ADH1B, and ADH1C genotypes in asians: A literature review. Alcohol Research & Health,30(1), 22-27.
- Weathermon, R. & Crabb, D.W. (1999). Alcohol and medication interactions. Alcohol Research & Health, 23(1), 40-54.