Gene Description

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Gene Description

UGT1A1

The uridine diphosphate glucuronosyltransferase (UGT) 1A1 is essential for the elimination of bilirubin, the main byproduct of heme catabolism. Reduced UGT1A1 activity results in elevated level of bilirubin in blood and tissues, which may cause jaundice, yellow discoloration of the skin and eyes.1 Atazanavir, indicated for human immunodeficiency virus type 1 (HIV-1), inhibits UGT1A1. The atazanavir-caused jaundice may result in premature discontinuation of atazanavir. The reduced function UGT1A1 alleles are strongly associated with increased risks of atazanavir premature discontinuation.2,3 Therefore, the Clinical Pharmacogenetics Implementation Consortium (CPIC) recommends an alternative agent for UGT1A1 poor metabolizer, particularly where jaundice would be a concern to the patient.3

 

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References
  1. Kadakol A, et al. Genetic Lesions of Bilirubin Uridine-diphosphoglucuronate Glucuronosyltransferase (UGT1A1) Causing Crigler-Najjar and Gilbert Syndromes: Correlation of Genotype to Phenotype. Mutat. 2000;16:297-306.
  2. Zhang D, et al. In Vitro Inhibition of UDP Glucuronosyltransferases by Atazanavir and Other HIV Protease Inhibitors and the Relationship of this Property to In Vivo Bilirubin Glucuronidation. Drug Metab. Dispos. 2005;33:1729-39.
  3. Gammal RS, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for UGT1A1 and Atazanavir Prescribing. Clin Pharmacol Ther. 2016;99(4):363-9.