1. ¹Department of Medicine, University of Chicago, Chicago, IL, USA
2. ²Department of Human Genetics, University of Chicago, Chicago, IL, USA
3. ³Committee on Clinical Pharmacology and Pharmacogenomics, University of Chicago, Chicago, IL, USA
4. ⁴Cancer Research Center, University of Chicago, Chicago, IL, USA

Correspondence: Dr F Innocenti, Section of Hematology-Oncology, Department of Medicine, University of Chicago, 5841 S, Maryland Avenue, MC2115, Chicago, IL 60637, USA; E-mail: finnocen@medicine.bsd.uchicago.edu

Received 26 November 2006; Revised 18 February 2007; Accepted 15 March 2007; Published online 17 April 2007.

Abstract

Experimental evidence suggests HNF1 regulates UGT expression. This study investigates (1) whether the variability in HNF1 expression is associated with the variability in UGT1A1, UGT1A9 and UGT2B7 expression in human livers and (2) the functionality of 12 HNF1 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 HNF1 mRNA levels and UGT genotype predicts variance in UGT expression to a higher extent than UGT genotype alone. None of the HNF1 polymorphisms studied, however, seem to have an effect on HNF1, UGT1A1, UGT1A9 and UGT2B7 expression, ruling out their functional role. Our data provide evidence for HNF1 being a determinant of UGT1A1, UGT1A9 and UGT2B7 mRNA expression. However, the amount of UGT intergenotype variability explained by HNF1 expression appears to be modest, and further studies should investigate the role of multiple transcription factors.