Aldehyde Dehydrogenase polymorphism

We had previously discussed the alcohol dehydrogenase genetic polymorphism, and had pointed out that among the Han Chinese, there is a high frequency of a genetic variant of alcohol dehydrogenase that allowed a faster conversion of ethanol to acetaldehyde. Acetaldehyde is the chemical that is thought to be responsible for not only the unpleasant effects of alcohol consumption (headaches, flushing etc) but is also thought to be the cause of tissue damage.

There is another enzyme that is responsible for the conversion of aldehyde dehydrogenase to acetic acid. This is called aldehyde dehydrogenase (ALDH). ALDH itself is subject to a genetic polymorphism where the genetic variant ALDH2*2 produces a slower enzyme. Among Han Chinese, the frequency of the ALDH2*2 variant is about 30%.

Among Han Chinese therefore, there is a significant number of individuals who will convert alcohol very quickly to acetaldehyde, and then have a slower removal of acetaldehyde. These individuals build up acetaldehyde concentrations in the blood very rapidly after consumption of alcohol. These individuals are the ones we recognize at drinking parties, who turn red very quickly after low consumption of alcohol.

A recent editorial in Human Genomics 3(2) 2009 highlights the risk this polymorphism poses with respect to the development of esophageal cancers.