CYP2E1 Genetic Variants: Breaking down alcohol and more

The body has many interesting and wonderful ways of getting rid of the toxins that we take in every day. We detoxify substances in a two-part system, breaking down the toxicants and then making them water soluble for excretion.

The CYP2E1 enzyme is part of the phase I detoxification system. Its responsibilities include getting rid of some cancer-causing substances and metabolizing alcohol at high levels of consumption. Genetic variants in this gene can increase the risk of certain cancers and of Tylenol poisoning. Members will see their genotype report below, plus additional solutions in the Lifehacks section. Join today 

What does the CYP2E1 gene do?

The CYP2E1 gene encodes an enzyme involved in the metabolism of several important drugs as well as the conversion of ethanol to acetaldehyde.

For example, the commonly used drug acetaminophen (Tylenol) is partially metabolized with this enzyme.

CYP2E1 also helps with the breakdown or activation of several anesthetics, as well as several industrial products including benzene and ethylene glycol.

Breaking down toxicants:

CYP2E1 metabolizes alcohol in the liver, in certain situations.

The enzyme is induced by ethanol when chronically consumed or when a lot of alcohol is consumed at once. Low levels of alcohol in occasional drinkers metabolize mainly through the alcohol dehydrogenase enzyme; higher levels of alcohol induce CYP2E1.[ref]

In fact, research shows that it is the increase in the CYP2E1 enzyme  that allows alcoholics to metabolize more alcohol. When alcohol breaks down, it becomes the toxic substance, acetaldehyde, and needs to be eliminated using other enzymes.

CYP2E1 is also involved in the metabolism of acrylamide, which is produced through the Maillard reaction when food is cooked. Examples of acrylamide formation in food would be in toast, french fries, potato chips, cookies, toasted breakfast cereal. Acrylamide can be carcinogenic (cancer-causing), so it is important to metabolize and get rid of it quickly.

When it comes to breaking down drugs, the CYP2E1 enzyme is important in metabolizing acetaminophen and chlorzoxazone (muscle relaxant).

CYP2E1 in the brain:

Nicotine also induces the CYP2E1 enzyme in the brain. This may explain why smokers who also drink a lot can have a higher rate of alcohol metabolism. CYP2E1 catalyzes about 20% of alcohol metabolism in the brain.[ref]

In addition to metabolizing substances that we take into the body, the CYP2E1 enzyme is important in breaking down endogenous substances such as fatty acids and ketone bodies.[ref]

Obesity and CYP2E1:

Similar to what is seen in increased alcohol consumption, people who are obese have an increased amount of CYP2E1 enzyme. This can be important for the correct dosages of medications that are metabolized with CYP2E1.[ref]


CYP2E1 Genotype Report:

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There are several variants of the CYP2E1 gene that are currently being studied.  While these variants play a role in increasing or decreasing this enzyme, factors such as alcohol usage or smoking may play a larger role for CYP2E1.

Keep in mind when it comes to cancer risk that the metabolites produced by CYP2E1 are likely to be the problem. Thus, a decrease in cancer risk could mean a decreased conversion (lower CYP2E1) of the initial substance into the metabolite.

Check your genetic data for rs2031920 (23andMe v4, v5; AncestryDNA):

  • T/T: CYP2E1 (Rsal) – decreased relative risk of lung cancer[ref][ref]  less likely to die from alcohol poisoning[ref] decreased risk of oral cancers[ref] decreased risk of liver cancer[ref]
  • C/T: Carrier of one CYP2E1-Rsal allele – slightly decreased risk of lung cancer; decreased risk of oral cancers, liver cancer
  • C/C: typical

Members: Your genotype for rs2031920 is .

Check your genetic data for rs3813867 (23andMe v5; AncestryDNA)

  • G/G: typical
  • C/G: Carrier of one Pstl allele, slightly decreased risk of lung cancer; decreased risk of oral cancer
  • C/C: Carrier of two Pstl alleles; possibly less likely to die from alcohol poisoning[ref] slightly decreased risk of lung cancer[ref] decreased risk of oral cancer[ref] increased risk of low birth weight babies when the mother is exposed to disinfection byproducts[ref]

Members: Your genotype for rs3813867 is .

 

Check your genetic data for rs2515641 (23andMev4, v5; AncestryDNA):

  • T/T: decreased CYP2E1 function, could affect acetaminophen metabolism[ref]
  • C/T: somewhat decreased function
  • C/C: typical

Members: Your genotype for rs2515641 is .

 


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About the Author:
Debbie Moon is the founder of Genetic Lifehacks. Fascinated by the connections between genes, diet, and health, her goal is to help you understand how to apply genetics to your diet and lifestyle decisions. Debbie has a BS in engineering and also an MSc in biological sciences from Clemson University. Debbie combines an engineering mindset with a biological systems approach to help you understand how genetic differences impact your optimal health.