This test detects genetic variants that affect alcohol metabolism. Individuals that carry these variants increase their risk of unpleasant side effects and serious health complications if they consume alcohol.

• Immediate reactions: facial flushing, nausea, dizziness, headaches, increased heart rate, insomnia, severe hangovers
• Increased risk of esophageal cancer: 10X increased risk for moderate drinkers and up to a 90X increased risk for heavy drinkers
• Cardiovascular problems
• Memory loss
• Mental confusion
• Psychological issues

How is alcohol metabolized?
The chemical name for the alcohol we consume is ethanol. Several processes can metabolize ethanol, but two enzymes break down the majority in a two-step process. Alcohol dehydrogenase (ADH) converts ethanol to acetaldehyde in the first step of alcohol metabolism (predominantly in the liver). Acetaldehyde is a toxic chemical, but is usually only short-lived, as it is quickly converted to acetate by aldehyde dehydrogenase (ALDH) in the second step of alcohol metabolism. Acetate is easily broken down to carbon dioxide and water.

Genes affecting alcohol metabolism
Individuals with genetic variants in the ADH1B, ADH1C and ALDH2 genes either produce acetaldehyde too quickly or are unable to eliminate it quickly enough. This results in a dangerous buildup of toxic acetaldehyde in the body after consumption of just moderate amounts of alcohol.

• ADH1B and ADH1C encode two members of the ADH family – the enzyme responsible for the conversion of ethanol to acetaldehyde (first step of alcohol metabolism). Genetic variants that increase ADH activity result in rapid build up of acetaldehyde.
• ALDH2 encodes a member of the ALDH family – the enzyme responsible for the conversion of acetaldehyde to acetate (second step of alcohol metabolism). A common variation in this gene decreases ALDH activity, slowing the removal of the toxic acetaldehyde.

Health risks for heterozygotes
Individuals that inherit two different variants (or alleles) of a particular gene are known as heterozygotes for that particular gene. The variants of the ADH1B, ADH1C and ALDH2 genes have a cumulative affect. For example, an individual with two slow ALDH2 alleles has zero detectable ALDH enzyme activity and will suffer from more severe side effects, compared to an individual that has one slow ALDH2 allele and one fast ALDH2 allele (ALDH2 heterozygote). ALDH2 heterozygotes have 30-50% of the ALDH activity compared to individuals that have two fast ALDH2 alleles.

Heterozygotes may be at increased risk of alcohol-related health complications, as their side effects are often just viewed as irritating or embarrassing (e.g. a mild alcohol flush), but not enough to prevent them from drinking alcohol. Several recent studies of Asian populations have shown that ALDH2 heterozygotes often still consume large amounts of alcohol, and some even take antihistamines to reduce the flush symptoms. Unfortunately this continued alcohol consumption considerably increases their risk of health issues – e.g. an approximately 10-fold increased risk of esophageal cancer for moderate drinkers and up to a 90-fold increased risk for heavy drinkers.