1,086
Views
114
CrossRef citations to date
0
Altmetric
Review Article

UGT genomic diversity: beyond gene duplication

, , , &
Pages 24-44 | Published online: 26 Oct 2009
 

Abstract

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.

Acknowledgements

Some of the work presented in this article was supported by the Canadian Institutes of Health Research (CIHR grants MOP-42392 and MOP-84223), The Natural Sciences and Engineering Research Council of Canada (NSERC), and The Canada Research Chair Program (CG). EL is a recipient of a CIHR clinician-scientist award. JB and VM are recipients of a PhD studentship award from the CIHR and Le Fonds de la recherche en santé du Québec (FRSQ), respectively. CG holds a Canada Research Chair in Pharmacogenomics.

Declaration of interest: No conflict of interest.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.