Tissue Distribution and Relative Gene Expression of UDP-Glucuronosyltransferases (2B7, 2B15, 2B17) in the Human Fetus

UDP-glucuronosyltransferases (UGTs) catalyze phase II conjugation reactions and play an important role in the inactivation and elimination of several drugs. It is well known that the UGT activity in fetal livers is low compared with the UGT activity in adult livers. In this study the mRNA expression levels of the three human subfamilies, 2B7, 2B15, and 2B17, were determined in 20 adult and 60 fetal liver tissue specimens. The expression profile in fetal kidneys (N = 43), adrenals (N = 46), and lungs (N = 37) was also determined. All fetal and adult samples were genotyped for the UGT2B17 deletion polymorphism. Adult liver contained 13-36 times higher levels of UGT2B mRNAs as compared with fetal livers. UGT2B7 was most abundant in fetal lungs and kidneys, whereas UGT2B15 and UGT2B17 were predominant in the liver. There was a significant correlation between UGT2B7 expression levels in lungs and kidneys, whereas for the other UGT2Bs no correlation between the different tissues was observed. Fetuses expressing two UGT2B17 alleles (ins/ins) displayed significantly higher levels of UGT2B17 mRNA compared to ins/del fetuses in lungs, whereas in the other tissues no gene dose-effect was observed.