Update on tools for evaluation of uridine diphosphoglucuronosyltransferase polymorphisms.
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.


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.
Argikar
Upendra A
UA
Novartis Institutes for BioMedical Research, Inc., 250 Massachusetts Avenue, Cambridge, MA 02139, USA.
Iwuchukwu
Otito F
OF
Nagar
Swati
S
D000818:Animals; D014453:Glucuronosyltransferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000378:metabolism; D010597:Pharmacogenetics / Q000379:methods*; D011110:Polymorphism, Genetic / Q000235:genetics*; D013379:Substrate Specificity
D007527:Isoenzymes; D004364:Pharmaceutical Preparations; D014453:Glucuronosyltransferase