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Uridine Diphosphate Glucuronosyltransferase 1A1 (UGT1A1)

PG4KDS Implemented Genes

UGT1A1 is an enzyme that breaks down medicines and also removes a substance called bilirubin from the body. Bilirubin is made in the body when red blood cells break down through a natural process.

Some people have a genetic tendency to make low levels of UGT1A1; these people may need a lower dose of certain medications because the low level of UGT1A1 puts them at risk for unusually high levels of some medications, or the low level of UGT1A1 means that their bilirubin levels get unusually high when they take certain medicines.

Some medicines may interfere with UGT1A1’s ability to do its job at getting rid of bilirubin. One such medicine is atazanavir. Atazanavir stops UGT1A1 from removing bilirubin from the 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 goes away when atazanavir is stopped. Like many medicines, how well atazanavir works and its side effects can be different from person to person.

Patients can be divided into 3 genotype metabolizer categories based on the function of UGT1A1; this information is used by clinicians to help guide drug therapy decisions.

Priority genotypes

  • Poor metabolizers – These patients have decreased UGT1A1 enzyme (30% of normal function) and may require different medicines or different doses of medicines. This genotype is generally indicative of Gilbert syndrome (for more information, please see About 15 in 100 people fall into this category.
    • Drugs that may need to be avoided:
      • Atazanavir. Consider using an alternative regimen that does not contain atazanavir, particularly if jaundice would be of concern to the patient.
    • Another drug, irinotecan, may require a dose adjustment if used at doses above 250 mg/m2/dose. At St. Jude, we do not routinely use such high doses; therefore dose adjustment based on UGT1A1 function is usually not required.
    • Drugs that may need to have their doses decreased:
      • Belinostat: If belinostat is used in a patient who is a UGT1A1 poor metabolizer, a dose reduction from the normal dose may be necessary.

Routine Genotypes

  • Normal metabolizers – These patients have normal working UGT1A1 enzyme. No changes to prescribing are needed based on this result. About 50 in 100 people fall in this category.
  • Intermediate metabolizers – These patients have slightly reduced UGT1A1 enzyme function. Currently, there are no known changes to prescribing are needed based on this result. About 40 in 100 people fall in this category.  

More information for patients

More information for healthcare professionals

Legal Disclaimer: This page is intended to provide implementers with guidance on establishing a clinical pharmacogenetic program at their institution. Information contained on this page is for information and educational purposes only. Although reasonable efforts have been made to ensure that the information provided on this page is current, complete and, where appropriate, based on scientific evidence, St. Jude Children's Research Hospital makes no assurances as to whether the provided information will at all times be current or complete. St. Jude Children's Research Hospital, in offering this document, is not providing medical advice or offering a consultative opinion, and is not establishing a treatment relationship with any given individual. You, therefore, should not substitute information contained herein for your own professional judgment, nor should you rely on information provided herein in rendering a diagnosis or choosing a course of treatment for a particular individual.