Can This Alcohol Metabolizing Gene Influence Your Alcohol Consumption? (ADH1B)

The ADH1B gene encodes for part of an enzyme named Alcohol Dehydrogenase (ADH), which is involved in the breakdown of alcohol in the liver.

ADH is responsible for the first step in this breakdown, where drinking alcohol is changed into potentially toxic acetaldehyde.

The ADH1B gene encodes an enzyme involved in the conversion of alcohol into potentially toxic acetaldehyde.

ADH1B variants are thought to influence alcohol consumption and alcohol dependence. Each variant produces an ADH enzyme that is capable of breaking down alcohol at a different rate.

Certain ADH1B variants produce a more active ADH, and more active ADH increases the rate at which alcohol is converted to acetaldehyde. This can lead to a build-up of toxic acetaldehyde following alcohol consumption, which can have negative effects such as [R, R]: 

• Flushing
• Sweating
• Nausea
• Accelerated heart rate 
• Vomiting

These negative ‘hangover’ effects may discourage ADH1B variant carriers from drinking alcohol. This is in comparison to non-variant carriers, who can drink alcohol without experiencing these symptoms [R, R].

ADH1B variants impact the activity of ADH enzymes, which may lead to negative effects that influence overall alcohol consumption.

rs1229984

Carrying a ‘T’ allele of rs1229984, a SNP in the ADH1B gene, can result in a 70- to 80-fold increase in the rate of conversion of alcohol to acetaldehyde following alcohol consumption. The  ‘T’ allele of rs1229984 can also cause side effects, including migraines, flushing, and breathlessness [R, R, R].

The ‘T’ variant of rs1229984 is particularly common in East Asians, where it is also associated with lower alcohol consumption and negative reactions to drinking alcohol, such as flushing [R, R, R].

On the other hand, several studies have associated carrying a ‘C’ allele of rs1229984, a SNP in the ADH1B gene, with an overall increase in alcohol drinking. This is relative to carriers of the ‘T’ allele, which has been linked to a reduced risk of alcohol dependence [R, R, R].

rs2066702

A study found that carriers of the ‘A’ allele of this variant felt more tired and had an accelerated heart rate after drinking alcohol [R].

Two genome-wide studies, of more than 69,000 people combined, found a significant protective effect for carrying an ‘A’ allele of the SNP rs2066702 on alcohol dependence in African-Americans. There are additional studies also confirming the link [R, R, R].

rs1042026

Two studies, one of almost 3000 people in China and another of around 4600 Australian twins, found a significant relationship between carrying a ‘C’ allele of rs1042026 and reduced alcohol consumption [R, R].

Carriers of ADH1B variants are more likely to experience adverse effects when drinking, and as a result are less likely to consume alcohol than non-carriers.

It’s important to mention that there are also conflicting studies which have found no association between ADH1B variant carriers and alcohol dependence or breakdown [R, R].

There are several reasons for these discrepancies.

First, there are many variants in different ADH genes that affect ADH enzyme activity and ADH1B is only one of them. 

Next, studies have found that the environment often plays a greater role in drinking habits than genetics, for example peer pressure and social drinking [R, R].  

For example, several environmental factors are known to interact with ADH1B genetic risk factors and in some instances, they oppose the prospective effects of the genotype [R, R, R, R]:

• Marital status
• Religion
• Parental strictness

ADH1B gene variants are only a part of the equation when it comes to alcohol consumption. Other genes and environmental factors also play a role.

Certain ADH1B variants have been linked to throat cancer [R, R]. This is because acetaldehyde has a direct negative impact on DNA. 

People with ADH1B variants (‘T’ allele for rs1229984, ‘C’ allele for rs1042026) may have a lower risk of throat cancer because they tend to drink less alcohol [R, R, R].

The drug Antabuse (Disulfiram) was developed to imitate the hangover effects of ADH1B variants as a treatment for alcohol dependence, and has since been associated with a lower risk of cancer [R].

On the other hand, heavy drinkers carrying ADH1B variants may be more likely to develop throat cancer than heavy drinkers without those variants. There is evidence that variants in other genes that increase acetaldehyde levels (ADH1C) increase the risk of throat cancer in heavy drinkers [R].

ADH1B variants may provide relative protective effects on risk of cancer due to reduced alcohol consumption. However, heavy drinking may result in an increased risk of cancer for variant carriers.

SNP Summary and Table

ADH1B rs1229984

• ‘TT’ = Associated with an accelerated conversion of alcohol into acetaldehyde. May be associated with flushing, nausea, and worse hangovers when drinking, often resulting in lower alcohol consumption [R, R]
• ‘CT’ = Associated with an accelerated conversion of alcohol into acetaldehyde. May be associated with flushing, nausea, and worse hangovers when drinking, often resulting in lower alcohol consumption  [R, R]
• ‘CC’ = Associated with normal conversion of alcohol into acetaldehyde. May be associated with increased risk of alcoholism [R]

91% of East Asians carry a copy of the ‘T’ allele. The ‘T’ allele is much less common in the rest of the world, where less than 10% are carriers [R]. 

ADH1B rs2066702

• ‘AA’ = Associated with accelerated conversion of alcohol into acetaldehyde. May be associated with flushing, nausea, and worse hangovers when drinking, often resulting in lower alcohol consumption [R]
• ‘AG’ = Associated with accelerated conversion of alcohol into acetaldehyde. May be associated with flushing, nausea, and worse hangovers when drinking, often resulting in lower alcohol consumption  [R]
• ‘GG’ = Associated with normal conversion of ethanol to acetaldehyde. May be associated with an increased risk of alcoholism [R]

The ‘A’ allele is mainly in Africans and African Americans, where 34% of individuals carry the ‘A’ allele. 4% of Native Americans also carry the ‘A’ allele. The ‘A’ allele is not typically present outside of these groups [R].

ADH1B rs1042026 

• ‘CC’ = Associated with lower alcohol consumption [R, R]
• ‘CT’ = Associated with lower alcohol consumption [R, R]
• ‘TT’ = Associated with normal alcohol consumption [R, R]

Roughly 53% of individuals carry a copy of the ‘C’ allele. This allele is more common in East Asians, where 97% of people have it, and South Asians, where 79% are carriers [R].