DNA Alcohol Risk Test

Alcohol response
Alcohol consumption is a common social activity for many people and a way to relax. However, not everyone is able to efficiently metabolize alcohol and it can cause adverse reactions and health problems. These reactions can include facial flushing (characterized by a warm, red and itchy face and neck), nausea, dizziness, headaches, increased heart rate, insomnia, severe hangovers and an overall feeling of physical discomfort. Alcohol–related health issues include increased cancer risks, cardiovascular problems and psychological issues. Individuals that suffer from unpleasant side effects have a decreased likelihood of excess alcohol consumption and developing alcohol dependence (alcoholism), predominantly due to the discomfort they suffer from alcohol consumption.

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 usually only short-lived and is converted to acetate by aldehyde dehydrogenase (ALDH). Acetate is easily broken down to carbon dioxide and water.

Effects of acetaldehyde
The toxic acetaldehyde produced from the first metabolic step is the major cause of adverse reactions to alcohol. Individuals who have either increased ADH activity (a fast first step from ethanol to acetaldehyde) or decreased ALDH activity (a slow second step from acetaldehyde to acetate) suffer from a build up of acetaldehyde. This chemical affects multiple cells and organs within the body, leading to the side effects described above.

Although alcoholics are less likely to carry the genetic variations that are associated with increased ADH activity or decreased ALDH activity, they are at a high risk of acetaldehyde poisoning due to their excess alcohol consumption. Many alcoholics suffer from mental confusion, memory loss and psychological symptoms (e.g. depression, agitation and anxiety) because of the acetaldehyde damage to their neurons. Individuals that are genetically predisposed to an accumulation of acetaldehyde may also suffer from these long-term effects, even if only small quantities of alcohol are consumed.

Acetaldehyde is also linked to an increased risk of esophageal cancer – the sixth most common cause of cancer-related death worldwide. Individuals that carry one or more genetic variants that cause an accumulation of acetaldehyde have an increased risk of esophageal cancer, and the risk is considerably higher if these individuals are also smokers and/or drink alcohol. Recent studies have also indicated an increased risk between genetically prone individuals and other health complications, including different cancers, cardiovascular issues and strokes.

Genes affecting alcohol metabolism:

ADH1B and ADH1C
The ADH1B and ADH1C genes encode two members of the alcohol dehydrogenase (ADH) family – the enzyme responsible for the conversion of ethanol to acetaldehyde (first step of alcohol metabolism). Genetic variants that increase the ADH activity increase the likelihood of adverse reactions to alcohol due to higher levels of acetaldehyde. These variants are also associated with a decreased risk of alcoholism. Changes in these enzymes do cause some facial flushing, but are more commonly associated with the other side effects.

ALDH2
The ALDH2 gene encodes a member of the aldehyde dehydrogenase (ALDH) family – the enzyme responsible for the conversion of acetaldehyde to acetate (second step of alcohol metabolism). A common variation in this gene decreases the ALDH activity, slowing the removal of the toxic acetaldehyde. This variant is the genetic change most commonly associated with intense facial flushing, known as the “Alcohol Flush” response.

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.

Who should take this genetic analysis?
This simple genetic analysis can explain why affected individuals suffer from unpleasant side effects even after consuming only a small quantity of alcohol. It is very useful to identify individuals that are at increased risk of health complications (e.g. esophageal cancer and liver disease). These at-risk individuals can minimize their health risks by eliminating their alcohol intake. This analysis can also be beneficial for individuals who have a family member who suffers from alcohol dependency. An understanding of the genetic factors contributing to this problem allows individuals to obtain support and avoid environmental factors that influence the risk of alcoholism.