Experimental evidence suggests HNF1α regulates UGT expression. This study investigates (1) whether the variability in HNF1α expression is associated with the variability in UGT1A1, UGT1A9 and UGT2B7 expression in human livers and (2) the functionality of 12 HNF1α 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 HNF1α mRNA levels and UGT genotype predicts variance in UGT expression to a higher extent than UGT genotype alone. None of the HNF1α polymorphisms studied, however, seem to have an effect on HNF1α, UGT1A1, UGT1A9 and UGT2B7 expression, ruling out their functional role. Our data provide evidence for HNF1α being a determinant of UGT1A1, UGT1A9 and UGT2B7 mRNA expression. However, the amount of UGT intergenotype variability explained by HNF1α expression appears to be modest, and further studies should investigate the role of multiple transcription factors.
ASJC Scopus subject areas
- Molecular Medicine