Pharmacogenomics of human uridine diphospho-glucuronosyltransferases (UGTs) and clinical implications

Glucuronidation, mediated by UDP-glucuronosyltransferase enzymes (UGTs), is a major phase II biotransformation pathway and, complementary to phase I metabolism and membrane transport, one of the most important cellular defense mechanism responsible for the inactivation of therapeutic drugs, other xenobiotics and numerous endogenous molecules. Individual variability in UGT enzymatic pathways is significant and may have profound pharmacological and toxicological implications. Several genetic and genomic processes are underlying this variability and are discussed in the context of drug metabolism and diseases such as cancer.