The UGT family of enzymes is responsible for an important part of phase II detoxification. In this article, I’ll explain what the UGT enzymes do in the body, how your genes impact this part of detoxification, and lifestyle factors that can increase or decrease this detox process.
Brief background: When foreign substances enter the body, such as pollutants or prescription medications, the body breaks the substances down and eliminates them. This whole process is referred to as phase I and phase II detoxification. Phase I detoxification uses the CYP enzymes to oxidize the toxic substance. Then in phase II, the toxic substance is altered again to make it water-soluble. This allows your body to easily excrete the substance.
The UDP-glucuronosyltransferase (abbreviated UGT) enzymes facilitate a glucuronidation reaction. This term means that one of the UGT enzymes helps make a substance more water-soluble for excretion through urine or feces.
This is important because the phase I detoxification intermediates often cause oxidative stress or other problems in the body. You don’t want them hanging around, damaging cells or DNA. Thus, this phase II process needs to act in sync with phase I, making the substance water-soluble so that it can be quickly eliminated.
What is affected by glucuronidation?
Glucuronidation reactions are used by the body to inactivate and eliminate:
bilirubin (from the breakdown of old red blood cells)
There are many different genetic variants in the UGT family of enzymes. Thus, some people may be more sensitive to certain medications or have a harder time breaking down and eliminating substances such as BPA.
Odor detection, COVID loss of smell:
Interestingly, the UGT genes also interact with odor molecules in the nose. The UGT enzymes are expressed in the cells lining the nose. When an odor molecule is glucuronidated (using an UGT enzyme), it no longer activates odor receptors, thus turning off the signal to the brain that you smell something. This ‘turning off’ of the smell means that things you smell are more transient – instead of a constant signal that lasts for a long time. Something we can be grateful for when it comes to bad odors!
Why is this interesting? New research shows that the inability to smell things (anosmia) as a result of Covid-19 may be linked with genetic variants in the UGT genes. While the difference based on the specific SNP identified in the study isn’t big (11% increased relative risk of anosmia), the mechanism of action indicated by the genetic findings is interesting. And no, the SNP identified in the study is not in 23andMe or AncestryDNA data.[ref]
The UGT family of genes codes for the enzymes needed for glucuronidation. Variants in these genes are fairly common, and the variants can increase or decrease the body’s ability to detoxify substances through glucuronidation.
UGT1A1 involves the breakdown of bilirubin, estrogen, and several carcinogens. The body naturally creates bilirubin as it clears out aged red blood cells. The UGT1A1 enzyme is responsible for the final step in making bilirubin easy for the body to get rid of. It is excreted in bile and urine (it’s what makes your poop brown).
Gilbert’s Syndrome is associated with this gene and involves bilirubin not being broken down appropriately. This syndrome leads to periodical increases in the level of unconjugated bilirubin, especially in times of physical stress such as illness, intense exercise, or fasting. This is a fairly common disorder with symptoms that include periodic yellowing of the eyes, abdominal pain, and fatigue.
A common variant, known as UGT1A1*28, has associations with higher bilirubin levels in Caucasian and African populations. There are questions/discrepancies surrounding the validity of the data on this in older 23andMe versions, and the data is not found in newer 23andMe or AncestryDNA versions. If you have data from another source, look for rs3064744.
Check your genetic data for rs4148323 (23andMe v4, v5; AncestryDNA):
A/A: UGT1A1*6 – increased bilirubin level, Gilbert’s syndrome (in Asian and Indian populations)[ref][ref , possibly decreased estrogen metabolism[ref] may alter dosing for irinotecan (cancer drug)[ref]
A/G: Carrier of UG/T1A1*6 (somewhat reduced enzyme activity)
Members: Your genotype for rs4148323 is —.
Check your genetic data for rs4124874 (23andMe v4, v5; AncestryDNA):
Check your genetic data for rs35003977 (23andMe v4; AncestryDNA):
G/T: higher bilirubin, Gilbert’s syndrome possible
G/G: high bilirubin and possible Gilbert’s syndrome[ref]
Members: Your genotype for rs35003977 is —.
UGT1A6 also helps with transforming bilirubin, hormones, and certain drugs (aspirin, acetaminophen) into water-soluble metabolites for excretion. Studies on this gene also look at the variants in association with benzene poisoning.
Check your genetic data for rs17863783 (23andMev4, v5; AncestryDNA):
T/T: increased UGT1A6, protective against bladder cancer[ref ]
G/T: increased UGT1A6
Members: Your genotype for rs17863783 is —.
Check your genetic data for rs6714486 (23andMe v4 only)
How your genes influence BPA detoxification:
BPA, a chemical found in some plastics, has been linked to a variety of effects on people including obesity, insulin resistance, and epigenetic effects on the fetus. Genetics plays a role in how quickly you can eliminate BPA from your body.
Nrf2 Pathway: Increasing the body’s ability to get rid of toxins
The Nrf2 (Nuclear factor erythroid 2–related factor) signaling pathway regulates the expression of antioxidants and phase II detoxification enzymes. This is a fundamental pathway that is important in how well your body functions. Your genetic variants impact how well this pathway functions.
Phase I and Phase II detoxification
Learn how the different genetic variants in phase I and phase II detoxification genes impact the way that you react to medications and break down different toxins.
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Originally published Jun 3, 2015
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 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.