Hepatocyte nuclear factor-1alpha is a causal factor responsible for interindividual differences in the expression of UDP-glucuronosyltransferase 2B7 mRNA in human livers

Drug Metab Dispos. 2002 Jun;30(6):613-5. doi: 10.1124/dmd.30.6.613.

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/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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA-Binding Proteins*
  • Glucuronosyltransferase / genetics
  • Glucuronosyltransferase / metabolism*
  • Hepatocyte Nuclear Factor 1
  • Hepatocyte Nuclear Factor 1-alpha
  • Hepatocyte Nuclear Factor 1-beta
  • Humans
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Liver / enzymology
  • Liver / metabolism*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • DNA-Binding Proteins
  • HNF1A protein, human
  • HNF1B protein, human
  • Hepatocyte Nuclear Factor 1-alpha
  • Isoenzymes
  • Nuclear Proteins
  • RNA, Messenger
  • Transcription Factors
  • Hepatocyte Nuclear Factor 1
  • Hepatocyte Nuclear Factor 1-beta
  • Glucuronosyltransferase