Phase I Detoxification: CYP2E1

The CYP2E1 gene codes for an enzyme involved in the metabolism of several important drugs as well as the conversion of ethanol to acetaldehyde. For example, acetaminophen (Tylenol) is one commonly used drug which is partially metabolized with this enzyme.  CYP2E1 is also involved in the breakdown or activation of several anesthetics, as well as several industrial products including benzene and ethylene glycol.

CYP2E1 is also involved in alcohol metabolism. It is induced by ethanol, and variants of CYP2E1 may protect against alcohol-induced liver disease. Low levels of alcohol in occasional drinkers are metabolized through the ADH enzyme; higher levels of alcohol induce CYP2E1. [ref]  In fact, research shows that it is the increased CYP2E1 that allows alcoholics to metabolize more alcohol. Nicotine also induces CYP2E1 in the brain and may link to increased alcohol metabolism in smokers who also drink a lot.[ref]

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.


CYP2E1 Genetic variants:

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, environmental factors such as alcohol usage may play a larger role for CYP2E1.

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

  • T/T: CYP2E1 (Rsal) – slightly decreased risk of lung cancer [ref][ref] possibly less likely to die from alcohol poisoning [ref] more likely to develop alcoholism [ref]; decreased risk of oral cancer[ref]
  • C/T: Carrier of one CYP2E1-Rsal allele – slightly decreased risk of lung cancer; more likely to develop alcoholism; decreased risk of oral cancers
  • C/C: normal

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

  • G/G: normal
  • 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]

Check your genetic data for rs6413419 (23andMev4, v5; AncestryDNA):

  • A/A: CYP2E1*4 – combined with GSTM1 null, more problems with acrylamide [ref]
  • A/G: Carrier of one CYP2E1*4 allele
  • G/G: normal

 

Check your genetic data for rs2070676 (23andMe rv4. v5):

  • G/G: CYP2E1*1B – studied in Parkinson’s disease risk [ref]
  • C/G: Carrier of one CYP2E1*1B allele
  • C/C: normal

(note: plus orientation)

 

This is part of an ongoing series on the genes involved in detoxification.

More to read:
CYP2E1 overview
http://www.ncbi.nlm.nih.gov/pubmed/16141435/
Study showing that Vitamin C and E mediate the effects of alcohol induced CYP2E1



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