What drugs are metabolized by UGT1A1?
Many exogenous substances, mutagenic xenobiotics and therapeutic drugs are UGT1A1 substrates. Examples of therapeutic drug substrates of UGT1A1 are: irinotecan (SN-38), acetaminophen (paracetamol), carvedilol, etoposide, lamotrigine and simvastatin [1-3].
What is UGT1A1 gene?
The UGT1A1 gene belongs to a family of genes that provide instructions for making enzymes called UDP-glucuronosyltransferases. These enzymes perform a chemical reaction called glucuronidation, in which a compound called glucuronic acid is attached (conjugated) to one of a number of different substances.
What is UGT1A1 test?
The test is used to determine the Gilbert’s syndrome, Crigler-Najjar syndrome.
What is UGT1A1 * 28?
UGT1A1*1 is the wild-type allele associated with normal enzyme activity. The most common variant allele is UGT1A1*28, which is commonly found in African-Americans (0.42–0.45 allele frequency) and Caucasians (0.26–0.31), and is less common in Asian populations (0.09–0.16) (27, 28).
Where is UGT1A1 located?
The UGT1A1 enzyme, primarily found in the liver, is responsible for the gluronidation of bilirubin, converting it from the toxic form of bilirubin (unconjugated bilirubin) to its nontoxic, water-soluble form (conjugated bilirubin).
How long do side effects of irinotecan last?
You may experience the following symptoms while you are receiving a dose of irinotecan or for up to 24 hours afterward: runny nose, increased saliva, shrinking pupils (black circles in the middle of the eyes), watery eyes, sweating, flushing, diarrhea (sometimes called ‘early diarrhea’), and stomach cramps.
What chromosome is UGT1A1 on?
The UGT1A1 gene is part of a gene complex located on chromosome 2 that encodes several enzymes called uridine diphosphate (UDP)-glycuronosyl transferases.
Why UGT1A1 test is done?
UDP Glucuronosyltransferase 1A1 (UGT1A1) Genotyping Confirms suspected diagnosis of Gilbert syndrome or Crigler-Najjar syndrome. Dosage planning for individuals who will receive high-dose irinotecan, have a history of irinotecan sensitivity, or experience neutropenia while receiving irinotecan.
Where is UGT1A1 gene located?
Can I take irinotecan If I have UGT1A1?
Irinotecan Therapy and UGT1A1 Genotype. The FDA-approved drug label for irinotecan states that “when administered as a single-agent, a reduction in the starting dose by at least one level of irinotecan hydrochloride injection should be considered for patients known to be homozygous for the UGT1A1*28 allele.
What is UGT1A1 in colorectal cancer?
UGT1A1 predicts outcome in colorectal cancer treated with irinotecan and fluorouracil. [World J Gastroenterol. 2012] UGT1A1 predicts outcome in colorectal cancer treated with irinotecan and fluorouracil.
What is the UGT1A1*28 variant?
The UGT1A1*28variant is also associated with drug toxicity. Approximately 10% of the North American population is homozygous for the *28allele (*28/*28genotype, also known as UGT1A1 7/7genotype) and are at an increased risk of neutropenia following intravenous irinotecan therapy (28).
Can genetic testing be used to diagnose UGT1A1?
Genetic Testing. Genetic testing to determine the UGT1A1 status of patients is available ( 36 ). Genotyping is used to optimize irinotecan dosing to prevent side effects when treating patients with metastatic colorectal cancer, and may also be used as part of the management of Gilbert syndrome ( 36 ).