ALDH2 Gene and its Impact on Alcohol Metabolism

Alcohol consumption has been a part of human culture for centuries. However, it is also a leading cause of liver diseases, cancers, and other chronic illnesses worldwide.

This article is not about alcohol addiction, but more about the underlying genetic causes.

Why is alcohol metabolism important?

Alcohol metabolism is a complex process that involves several enzymes and pathways in the liver. And we all know that enzymes are encoded by genes in the DNA.

The enzyme that plays a crucial role in alcohol metabolism is called aldehyde dehydrogenase 2 (ALDH2).

In this article, we will discuss how the ALDH2 gene affects alcohol metabolism and the health implications of its dysfunction.

The ALDH2 Gene and Alcohol Metabolism

The ALDH2 gene is responsible for producing the ALDH2 enzyme, which is primarily found in the liver.

The ALDH2 enzyme breaks down acetaldehyde, a toxic byproduct of alcohol metabolism, into acetate.

Acetate is then broken down further into carbon dioxide and water, which are harmless byproducts that can be excreted by the body.

Acetaldehyde is a highly reactive and toxic substance that can cause DNA damage, oxidative stress, and other harmful effects in the body.

Individuals who have a functional ALDH2 gene produce sufficient levels of the ALDH2 enzyme, which enables them to break down acetaldehyde efficiently.

However, individuals who have a dysfunctional ALDH2 gene produce low levels of the ALDH2 enzyme or no enzyme at all, which leads to the accumulation of acetaldehyde in the body.

ALDH2 Gene Mutation

The ALDH2 gene mutation is a genetic condition that affects the function of the ALDH2 enzyme. The mutation occurs due to a change in the DNA sequence of the ALDH2 gene, which leads to a dysfunctional enzyme. Individuals who inherit a mutated ALDH2 gene from both parents have a severe form of the condition and cannot metabolize alcohol efficiently.

A previous study reported that ALDH2*2 homozygotes and heterozygotes had 18 and 5 times higher blood alcohol levels, respectively than ALDH2*1 homozygotes after drinking the same amount of alcohol.

Genotype	Effect on body
ALDH2*2 homozygotes	High blood alcohol levels
ALDH2*2 heterozygotes	Medium-high blood alcohol levels
ALDH21* homozygotes	Low blood alcohol levels

The most common ALDH2 gene mutation is the ALDH2*2 allele. It causes a 70-80% reduction in ALDH2 enzyme activity.

ALDH2 Gene in the population

The dysfunctional ALDH2 variant affects nearly 8% of the world population and is highly concentrated among East Asians.

As a result, individuals with the ALDH2*2 allele experience flushing, rapid heartbeat, and other unpleasant symptoms when they consume alcohol.

Health Implications of ALDH2 Gene Dysfunction

ALDH2 gene dysfunction can have several health implications, including:

Individuals with ALDH2 gene dysfunction are unable to break down acetaldehyde efficiently, which leads to its accumulation in the body.

Acetaldehyde is a highly reactive and toxic substance that can cause DNA damage, oxidative stress, and other harmful effects in the body.

The accumulation of acetaldehyde can lead to an increased risk of alcohol-related diseases, including liver diseases, cancers, and cardiovascular diseases.

Increased Risk of Alcohol Dependence

ALDH2 gene dysfunction has been linked to an increased risk of alcohol dependence. Individuals with dysfunctional ALDH2 genes may experience unpleasant symptoms when they consume alcohol, such as flushing, rapid heartbeat, and nausea.

These symptoms may discourage them from consuming alcohol initially, but repeated exposure can lead to tolerance and dependence.

Increased Risk of Adverse Drug Reactions

Several drugs, including some chemotherapy drugs and drugs used to treat heart diseases, require the ALDH2 enzyme to metabolize efficiently.

Individuals with ALDH2 gene dysfunction may be at an increased risk of adverse drug reactions due to the reduced ability to metabolize these drugs.

Impact on Fetal Development

Alcohol consumption during pregnancy can have severe consequences on fetal development. In individuals with dysfunctional ALDH2 genes, acetaldehyde can cross the placenta and accumulate in the fetal bloodstream.

Acetaldehyde exposure during fetal development can lead to fetal alcohol spectrum disorders (FASD), a group of conditions that can cause physical, behavioral, and intellectual disabilities.

Management of ALDH2 Gene Dysfunction

One of the advantages of understanding your genetic risk for alcohol-related health issues is that you can take measures to curb it.

Here are some recommendations if you have a faulty ALDH2 gene:

Going easy on the alcohol

Complete abstinence from alcohol may not be viable for many of us, but moderation can certainly help. Especially if you have learned from your detox report that you have the ALDH2*2 gene mutation

Talking to a counselor

Individuals with a family history of ALDH2 gene dysfunction should consider genetic counseling to assess their risk of inheriting the condition.

Getting some symptomatic Relief

Individuals who experience flushing, rapid heartbeat, or other unpleasant symptoms when they consume alcohol can take over-the-counter medications to manage their symptoms.

These medications include antihistamines, which can reduce flushing, and aspirin, which can reduce the risk of cardiovascular events.

Making some lifestyle changes

Try maintaining a healthy diet that is wholesome with a lot of vegetables, protein, and minerals,
Engage in regular exercise
Avoiding smoking.

Final Remarks

In conclusion, the ALDH2 gene plays a crucial role in alcohol metabolism, and its dysfunction can have severe health implications.

Individuals with dysfunctional ALDH2 genes should avoid alcohol consumption and adopt a healthy lifestyle to reduce the risk of alcohol-related diseases.

Genetic counseling can also help assess the risk of inheriting the condition.

Further research is needed to develop targeted therapies for individuals with ALDH2 gene dysfunction and to better understand the complex interplay between genetics and alcohol metabolism.