Aldehyde dehydrogenase gene, also known as ALDH2 or aldehyde dehydrogenase 2 family, encodes enzymes of aldehyde dehydrogenase family, which catalyze the oxidation of acetaldehyde to acetate. The gene is located on human chromosome 12.
Human bodies break down alcohol in two steps. First, alcohol is converted into acetaldehyde by ADH (enzyme alcohol dehydrogenase); then acetaldehyde is further oxidized into acetate by acetylaldehyde dehydrogenase. The acetate could then be hydrolyzed into carbon dioxide and water.
Acetaldehyde is toxic to human body, it may cause rapid heartbeat, nausea, sweating, dizziness and facial flush.
Mutations in aldehyde dehydrogenase gene cause acetaldehyde dehydrogenase deficiency. People experiencing such mutaions have less efficient acetaldehyde dehydrogenase breakdown and could result in a buildup of acetaldehyde after drinking. This will lead to facial flushing and other associated symptoms.
A well-known symptom casued by acetaldehyde deficiency is called Asian Flush, named after the fact that Asians particularly have higher possibilities to have mutations in aldehyde dehydrogenase gene (about 50% Asians experience this mutation).
The SNP site on aldehyde dehydrogenase gene is at the 110,726,149th bp (Chr12 110,726,149) on human chromosome 12, where there can be a change from G (normal) to A. Allele with G are known as ALDH2*1 while those with A are known as ALDH2*2.
ALDH2*1 allele encodes normal ALDH2 with normal function, whereas ALDH2*2 encodes an inactive enzyme. There are two main variants of aldehyde dehydrogenase gene. People with one copy of ALDH2*1 and one copy of ALDH2*2 will get facial flush after consuming alcohol more easily comparing to those with both copies of ALDH2*1, whereas people with two copies of ALDH2*2 are more likely to have a severe alcohol flush.
Acetaldehyde is listed as a class I carcinogen. People experiencing these mutations are at higher risk of developing esophageal cancer, most likely caused by acetaldehyde dehydrogenase deficiency and an increase of saliva acetaldehyde.
On the brightside, people with two copies of ALDH2*2 are less likely to drink alcohol because acetaldehyde produces unpleasant response.
At the SNP site of aldehyde dehydrogenase gene located at the Chr12 110,726,149, John has a GG (normal) genotype. In other words, John has two copies of ALDH2*1 alleles, which means he will have wild-type ALDH2 with normal enzymatic function, and acetaldehyde will be correctly oxidized into acetate. This suggests that John is not likely to suffer from symptoms of alcohol flush, or risks of having esophageal cancer in the future.
2. Yoshida A. (1985) Molecular abnormality and cDNA cloning of human aldehyde dehydrogenases.