A Novel Polymorphism in a Forkhead Box A1 (FOXA1) Binding Site of the Human UDP Glucuronosyltransferase 2B17 Gene Modulates Promoter Activity and Is Associated with Altered Levels of Circulating Androstane-3 alpha, 17 beta-diol Glucuronide
Dong Gui Hu, Dione Gardner-Stephen, Gianluca Severi, Philip A Gregory, Joanna Treloar, Graham G Giles, Dallas R English, John L Hopper, Wayne D Tilley, Peter I Mackenzie
Molecular Pharmacology | AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS | Published : 2010
UDP glucuronosyltransferase 2B17 is present in the prostate, where it catalyzes the addition of glucuronic acid to testosterone and dihydrotestosterone and their metabolites androsterone and androstane-3α,17β-diol. Hence, changes in UGT2B17 gene expression may affect the capacity of the prostate to inactivate and eliminate male sex hormones. In this work, we identify a prevalent polymorphism, -155G/A, in the proximal promoter of the UGT2B17 gene. This polymorphism modulates UGT2B17 promoter activity, because luciferase-gene reporter constructs containing the -155A allele were 13-fold more active than those containing the -155G allele in prostate cancer LNCaP cells. The -155G/A polymorphism i..View full abstract
Awarded by National Health and Medical Research Council of Australia
The work was supported by funding from the National Health and Medical Research Council of Australia [Grant 426705].