Hepatocyte nuclear factor-4α/γ and hepatocyte nuclear factor-1α as causal factors of interindividual difference in the expression of human dihydrodiol dehydrogenase 4 mRNA in human livers

Takeshi Ozeki, Yoshiki Takahashi, Kazuo Nakayama, Masato Funayama, Kazuo Nagashima, Takao Kodama, Tetsuya Kamataki

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

Human dihydrodiol dehydrogenase (DD) catalyses the oxidation of trans-dihydrodiols of polycyclic aromatic hydrocarbons and the reduction of several ketone-containing drugs. About 40-fold interindividual difference in DD activities has been noted. Recently, we found that transcriptional factors, hepatocyte nuclear factor (HNF)-1α, HNF-4α and HNF-4γ were essential for the expression of DD4 mRNA, which is a major form of DDs. Thus, to clarify a possible mechanism(s) underlying the interindividual difference in DD activities, we investigated the sequences of genes and the expression levels of mRNA for DD4 and HNFs in human livers. We found no clear relationship between the genotypes of DD4 and HNF genes and the expression levels of DD4 mRNA in the subjects. The expression level of DD4 mRNA significantly correlated with that of HNF-1α, HNF-4α or HNF-4γ. These results suggest that the expression level of DD4 mRNA is cooperatively regulated by the amounts of HNF-1α, HNF-4α and HNF-4γ.

Original languageEnglish
Pages (from-to)49-53
Number of pages5
JournalPharmacogenetics
Volume13
Issue number1
DOIs
Publication statusPublished - 2003 Jan

Keywords

  • Genetic polymorphism
  • Quantitative RT-PCR
  • Synergistic expression
  • Transcriptional regulation

ASJC Scopus subject areas

  • Genetics
  • Pharmacology, Toxicology and Pharmaceutics(all)

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