Hepatocyte nuclear factor-1alpha is a causal factor responsible for interindividual differences in the expression of UDP-glucuronosyltransferase 2B7 mRNA in human livers.
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/10(3) copies of beta-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)-1alpha, which regulates the expression of UGT2B7 gene. HNF-1alpha mRNA was expressed at a level ranging from 2.99 to 24.76 copies/10(6) copies of beta-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-1alpha (r = 0.786, p = 0.002), suggesting that HNF-1alpha is a factor limiting the expression of UGT2B7 mRNA and a causal factor responsible for an interindividual difference in human livers.
Toide
Kenji
K
Graduate School of Pharmaceutical Sciences, University of Kansas Medical Center, Kansas City, Kansas, USA.
Takahashi
Yoshiki
Y
Yamazaki
Hiroshi
H
Terauchi
Yoshiaki
Y
Fujii
Toshihiko
T
Parkinson
Andrew
A
Kamataki
Tetsuya
T
D004268:DNA-Binding Proteins; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism*; D051537:Hepatocyte Nuclear Factor 1; D051538:Hepatocyte Nuclear Factor 1-alpha; D051539:Hepatocyte Nuclear Factor 1-beta; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; C496487:HNF1A protein, human; C496495:HNF1B protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; D007527:Isoenzymes; D009687:Nuclear Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D051537:Hepatocyte Nuclear Factor 1; D051539:Hepatocyte Nuclear Factor 1-beta; D014453:Glucuronosyltransferase