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Vol. 30, Issue 6, 613-615, June 2002

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

Kenji Toide, Yoshiki Takahashi, Hiroshi Yamazaki, Yoshiaki Terauchi, Toshihiko Fujii, Andrew Parkinson, and Tetsuya Kamataki

Graduate School of Pharmaceutical Sciences,
Hokkaido University, Sapporo, Japan
(K.T., Y.Ta, H.Y., T.K.);
Department of Pharmacokinetics,
Dainippon Pharmaceutical Co., Ltd.
Osaka, Japan (Y.Te, T.F.);
Center for Environmental and Occupational Health,
University of Kansas Medical Center,
Kansas City, Kansas (A.P.)

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 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/106 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.


Copyright © 2002 by The American Society for Pharmacology and Experimental Therapeutics



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