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

研究成果: Article査読

11 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)49-53
ページ数5
ジャーナルPharmacogenetics
13
1
DOI
出版ステータスPublished - 2003 1月

ASJC Scopus subject areas

  • 遺伝学
  • 薬理学、毒性学および薬学(全般)

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