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UGT1A1 and medicines

 

When you take a medicine (drug), your body has to have a way to handle the medicine. One way is for enzymes to metabolize (break down) the medicine. Uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) is an enzyme that has the ability to break down medicines and also to remove a substance called bilirubin from your body. Bilirubin is made in the body when your red blood cells break down through a natural process.

Some medicines may interfere with UGT1A1’s ability to do its job. One medicine is atazanavir, a drug used to treat human immunodeficiency virus (HIV) infection. Atazanavir stops UGT1A1 from removing bilirubin from your body. As a result, people who take atazanavir may have higher levels of bilirubin in their blood, which can lead to yellowing of the eyes and skin. The medical word for this is “jaundice.” Although this effect may cause some people to worry about their appearance, this effect is usually not harmful and is reversible if atazanavir is stopped. Like many medicines, how well they work and their side effects can be different from person to person. Individuals whose UGT1A1 enzymes are working slowly may have a condition called Gilbert syndrome, which may or may not lead to jaundice, even in patients who aren’t taking medicines.

People with sickle cell disease whose UGT1A1 enzymes are working slowly may be at higher risk for developing jaundice and gallbladder problems, including gallbladder stones.

Pharmacogenetic testing

DNA is like a set of instructions for your body that can help decide how well your enzymes will work. Each person differs from another at the DNA (gene) level. This means that each person has small differences in the genes that code for enzymes. The part of DNA that instructs how well UGT1A1 enzymes will work is called the UGT1A1 gene. The study of how genes like UGT1A1 affect the way you break down and respond to medicines is called pharmacogenetics (FAR mah coh je NEH tiks).

Differences in your DNA that make up the UGT1A1 gene can change how well you are able to remove bilirubin and certain medicines from your body. By testing your DNA (with a pharmacogenetic test), we may find differences that can allow us to predict how well your UGT1A1 enzyme will work. The results of this test will help your doctor choose the correct type or dose of medicine to give you.

The results of your UGT1A1 pharmacogenetic test will likely place you into one of three groups:

  • Normal UGT1A1 function – People in this group have normal working UGT1A1 enzymes. Atazanavir may be prescribed based upon this UGT1A1 genetic test result. About 50 out of 100 people fall in this category.
  • Intermediate UGT1A1 function – This means there is one normal, functional copy of the gene and one reduced function copy of the gene. People in this group have slightly reduced UGT1A1 enzyme function. Atazanavir may still be prescribed based upon this UGT1A1 genetic test result. About 40 out of 100 people fall in this category.
  • Low UGT1A1 function – This means there are two copies of a reduced function gene which results in very reduced UGT1A1 function. This genotype has been associated with Gilbert syndrome. If people in this group take atazanavir, they are at high risk for having jaundice. It may be best to avoid atazanavir in patients with reduced UGT1A1 enzyme function. About 10 out of 100 people fall in this category. For more information about Gilbert syndrome, please refer to this website: ghr.nlm.nih.gov/condition/gilbert-syndrome.

UGT1A1 breaks down other medicines, including the cancer drug irinotecan. For more information about UGT1A1 and atazanavir, please go to www.stjude.org/pg4kds or https://CPICpgx.org.

Questions?

If you have questions about pharmacogenetic testing at St. Jude, call one of the Pharmaceutical Sciences research nurses at (901) 595-2482 or email pknurses@stjude.org. If you are calling from outside of the Memphis area, dial toll free 1-866-2ST-JUDE (1-866-278-5833), then dial extension 2482.


 

This document is not intended to take the place of the care and attention of your personal physician or other professional medical services. Our aim is to promote active participation in your care and treatment by providing information and education. Questions about individual health concerns or specific treatment options should be discussed with your physician.

St. Jude complies with health care-related federal civil rights laws and does not discriminate on the basis of race, color, national origin, age, disability, or sex.

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