UGT genomic diversity: beyond gene duplication.
The human uridine diphospho (UDP)-glucuronosyltransferase (UGT) superfamily comprises enzymes responsible for a major biotransformation phase II pathway: the glucuronidation process. The UGT enzymes are located in the endoplasmic reticulum of almost all tissues, where they catalyze the inactivation of several endogenous and exogenous molecules, including bilirubin, sex steroids, numerous prescribed drugs, and environmental toxins. This metabolic pathway is particularly variable. The influence of inheritable polymorphisms in human UGT-encoding genes has been extensively documented and was shown to be responsible for a fraction of the observed phenotypic variability. Other key genomic processes are likely underlying this diversity; these include copy-number variations, epigenetic factors, and newly discovered splicing mechanisms. This review will discuss novel molecular aspects that may be determinant to UGT phenotypes.
Guillemette
Chantal
C
Pharmacogenomics Laboratory, CHUQ Research Center and Faculty of Pharmacy, Laval University, Quebec City, Quebec, Canada. Chantal.Guillemette@crchul.ulaval.ca
Lévesque
Eric
E
Harvey
Mario
M
Bellemare
Judith
J
Menard
Vincent
V
D017398:Alternative Splicing / Q000235:genetics*; D000818:Animals; D002460:Cell Line; D020440:Gene Duplication; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D014644:Genetic Variation; D015894:Genome, Human; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D010597:Pharmacogenetics / Q000379:methods; D010641:Phenotype; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis
D012333:RNA, Messenger; D014453:Glucuronosyltransferase