Hepatocyte Nuclear Factor-1α Is a Causal Factor Responsible for Interindividual Differences in the Expression of UDP-Glucuronosyltransferase 2B7 mRNA in Human Livers

Open Access
Publisher Website
Google Scholar
Abstract
UDP-glucuronosyltransferase (UGT) 2B7 is one of the most important UGT isozymes expressed in human livers. This enzyme is reported to show more than 10-fold interindividual differences in its enzyme activities. Thus, the amounts of UGT2B7 mRNA in 12 human livers were quantified by quantitative reverse transcription-polymerase chain reaction. The amounts of UGT2B7 mRNA in the subjects ranged from 0.22 to 2.63 copies/103 copies of β-actin. A novel point mutation (−253G to A) found in this study did not affect the level of UGT2B7 mRNA in the subjects. To clarify a causal factor(s) determining the expression level of UGT2B7 mRNA, we examined the correlation between the amounts of mRNAs for UGT2B7 and hepatocyte nuclear factor (HNF)-1α, which regulates the expression of UGT2B7gene. HNF-1α mRNA was expressed at a level ranging from 2.99 to 24.76 copies/106 copies of β-actin in the subjects. The amounts of mRNAs for UGT2B7 expressed in these individual liver samples were highly associated with the amount of mRNA for HNF-1α (r = 0.786, p = 0.002), suggesting that HNF-1α is a factor limiting the expression of UGT2B7 mRNA and a causal factor responsible for an interindividual difference in human livers.