Phase 2 Detoxification – UGTs

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

UDP-glucuronosyltransferase (abbreviated UGT) creates a glucuronidation reaction, which is a big part of phase II detoxification.  Once a drug, toxin, or other substance is broken down in a phase I reaction (see the CYP genes), the Phase II reactions further alter the substance so that it can be excreted from the body.

UGT enzymes are important for getting rid of quite a few different medications as well as environmental chemicals such as BPA and other estrogen-mimicking compounds. These enzymes also are involved in our body’s natural process of eliminating bilirubin, estrogen metabolites, and other hormones.


There are quite a few genes involved in glucuronidation, and most are prefixed with UG/T.

UGT1A1 is involved in the breakdown of bilirubin, estrogen, and several carcinogens. Gilbert’s Syndrome is associated with this gene and involves bilirubin not being broken down appropriately.  One study in 2009 showed that the levels of UGT1A1 activity can be increased with cruciferous vegetables.  This may be one way that cruciferous veggies are protective against cancer.

Bilirubin, a substance that brings to mind jaundice in babies, is a breakdown product naturally caused in a body as it clears out aged red blood cells.  It is excreted in bile and the urine (this is what makes your poop brown).

UGT1A1 is also responsible for the breakdown of BPA (in plastics) [ref].

Note: There is a common variant that causes decreased UGT activity (Caucasians, Africans) called UGT1A1*28. It is not included in 23andMe data, so even if the information below shows that you have no UGT variants, this doesn’t give you the whole picture. In other words, if you carry a variant below, you know that you have decreased UGT1A1 activity, but if you don’t carry the variants below, you can’t assume that you have normal UGT1A1 enzyme activity.

Check your 23andMe results for rs4148323 (v4, v5):

  • A/A: UGT1A1*6 – increased bilirubin level, Gilbert’s syndrome in Asian populations
  • A/G: Carrier of UG/T1A1*6 (somewhat reduced enzyme activity)
  • G/G: normal

Check your 23andMe results for rs4124874 (v4, v5):

  •  G/G: UGT1A1*60[ref], reduced enzyme activity, increased bilirubin (Caucasian)[ref]
  •  T/T: normal

Check your 23andMe results for rs6742078 (v4, v5):

  •  T/T: reduced UGT1A1 activity, increased gallstone risk (males)[ref]
  •  G/G: normal

 UGT1A6 is also involved in transforming bilirubin, hormones, and certain drugs (aspirin, acetaminophen)  into water-soluble metabolites that can then be excreted from the body.  Studies on this gene also look at the polymorphisms in association with benzene poisoning.

Check your 23andMe results for rs887829 (v4, v5):

  •  T/T: higher serum bilirubin levels, protective against heart disease
  •  C/C: normal

Check your 23andMe results for rs17863783 (v4, v5):

  •  T-allele: protective against bladder cancer
  • G/G: normal

UGT1A9:

Check your 23andMe results for rs6714486 (v4 only)

  • A/A: higher activity [ref] [ref]
  • T/T: normal

 


Lifehacks:

Cruciferous vegetables cause your body to increase the production of UGT1A1. If you aren’t eating enough cruciferous veggies, supplements of I3C and DIM (diindolylmethane) are available. They are a specific part of cruciferous veggies that induce UGT1A1. [ref]

More to read:
UGT1a1 polymorphisms are important determinants of dietary carcinogen detoxification in the liver (2005)

Regulation of the UGT1a1 Bilirubin-Conjugating Pathway (2006)



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4 Comments on “Phase 2 Detoxification – UGTs

  1. Pingback: Genetic Lifehacks | ADHD, pesticides, and genetic polymorphisms

  2. Pingback: Detoxifying Phthalates:  Genes and Diet | Genetic Lifehacks

  3. This is very helpful! Thank you!
    Could you please fix the second link (for rs6742078) because the link is actually wrong (points to a different SNP query)?

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