TY - JOUR T1 - Hepatocyte Nuclear Factor-1α Is a Causal Factor Responsible for Interindividual Differences in the Expression of UDP-Glucuronosyltransferase 2B7 mRNA in Human Livers JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 613 LP - 615 DO - 10.1124/dmd.30.6.613 VL - 30 IS - 6 AU - Kenji Toide AU - Yoshiki Takahashi AU - Hiroshi Yamazaki AU - Yoshiaki Terauchi AU - Toshihiko Fujii AU - Andrew Parkinson AU - Tetsuya Kamataki Y1 - 2002/06/01 UR - http://dmd.aspetjournals.org/content/30/6/613.abstract N2 - 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 β-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)-1α, which regulates the expression of UGT2B7gene. HNF-1α mRNA was expressed at a level ranging from 2.99 to 24.76 copies/106 copies of β-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-1α (r = 0.786, p = 0.002), suggesting that HNF-1α is a factor limiting the expression of UGT2B7 mRNA and a causal factor responsible for an interindividual difference in human livers. The American Society for Pharmacology and Experimental Therapeutics ER -