Update on tools for evaluation of uridine diphosphoglucuronosyltransferase polymorphisms

Abstract

Background: The uridine diphosphoglucuronosyltransferase (UGT) superfamily of enzymes catalyzes conjugative metabolism of numerous endobiotics and xenobiotics. Pharmacogenetic variation has been reported in almost all UGT family members. Objective: To discuss tools available for evaluation of UGT polymorphisms. Methods: Literature search was done to include all relevant UGT polymorphism studies involving in vitro methods. Results/conclusions: Studies evaluating associations between UGT genotype and resultant phenotype are described. Mammalian cells transfected with variant UGT isoforms or variant promoters have been developed. Human liver tissue genotyped for UGT genetic polymorphisms has been successfully used. New techniques to conduct these studies include RNA inhibition and development of transgenic animal models. Challenges and opportunities in the preclinical evaluation of UGT genotype–phenotype correlations are discussed.

Keywords::

• genotype–phenotype correlation
• pharmacogenetics
• polymorphisms
• uridine diphosphoglucuronosyltransferase (UGT)