Studies of the UDP-glucuronosyltransferase enzymes family activity

Decreased activity of the UDP-glucuronyltransferase 1A1 (UGT1A1) is the cause of unconjugated hyperbilirubinemia in patients with Gilbert and Crigler-Najjar II syndromes, as well as the cause of adverse events when taking drugs. The main indicator of the reduced activity of the enzyme is an increase in plasma bilirubin, and the leading molecular genetic cause in the European population is the rs3064744 variant in the promoter of the UGT1A1 gene. However, the issue of directly measuring enzyme activity under various conditions is not addressed in the Russian literature. Objective. To summarize the data on molecular genetic, epigenetic, and age factors affecting the activity of UGT family enzymes. Materials and methods. We searched for Russian papers in the Cyberleninka and eLibrary scientific electronic libraries, and international publications in the PubMed and MEDLINE databases. Publications over the past 10 years on UGT family enzymes and their activity were selected for review. Also, selected early papers are included in the review as they contain important data. Results. Data on age-related, molecular genetic, and epigenetic factors affecting gene expression and the activity of UGT family enzymes involved in the metabolism of endogenous and exogenous substances were analyzed and summarized. Conclusion. Genetic and epigenetic factors underlying variable UGT expression were identified across tissues and patients. Increased knowledge of UGT helps predict and reduce the risk of adverse reactions in patients taking drugs metabolized by these enzymes.