Hepatocyte nuclear factor-1 alpha is associated with UGT1A1, UGT1A9 and UGT2B7 mRNA expression in human liver

Pharmacogenomics J. 2008 Apr;8(2):152-61. doi: 10.1038/sj.tpj.6500454. Epub 2007 Apr 17.

Abstract

Experimental evidence suggests HNF1alpha regulates UGT expression. This study investigates (1) whether the variability in HNF1alpha expression is associated with the variability in UGT1A1, UGT1A9 and UGT2B7 expression in human livers and (2) the functionality of 12 HNF1alpha variants using mRNA expression as phenotype. Controlling for known UGT variation in cis-acting elements known to affect UGT expression, we demonstrate that a combination of HNF1alpha mRNA levels and UGT genotype predicts variance in UGT expression to a higher extent than UGT genotype alone. None of the HNF1alpha polymorphisms studied, however, seem to have an effect on HNF1alpha, UGT1A1, UGT1A9 and UGT2B7 expression, ruling out their functional role. Our data provide evidence for HNF1alpha being a determinant of UGT1A1, UGT1A9 and UGT2B7 mRNA expression. However, the amount of UGT intergenotype variability explained by HNF1alpha expression appears to be modest, and further studies should investigate the role of multiple transcription factors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Gene Expression Regulation, Enzymologic*
  • Gene Frequency
  • Genotype
  • Glucuronosyltransferase / analysis
  • Glucuronosyltransferase / genetics*
  • Hepatocyte Nuclear Factor 1-alpha / analysis
  • Hepatocyte Nuclear Factor 1-alpha / genetics*
  • Humans
  • Liver / chemistry
  • Liver / enzymology*
  • Phenotype
  • Polymorphism, Genetic*
  • RNA, Messenger / analysis*

Substances

  • Hepatocyte Nuclear Factor 1-alpha
  • RNA, Messenger
  • UGT1A1 enzyme
  • UGT2B7 protein, human
  • Glucuronosyltransferase
  • UDP-glucuronosyltransferase 1A9