Role of HNF-1? in the regulation of UGT1A1, UGT1A9 and UGT2B7 MRNA expression

Abstract

Background The hepatocyte nuclear factor 1α (HNF-1α) is potentially involved in the regulation of the expression of UGT1A1, UGT1A9 and UGT2B7. A variant (79A>C) in HNF-1α has been associated with insulin resistance and glucose intolerance among nondiabetic individuals; however, its effect on HNF1-α function is not known. We aim to investigate the role of HNF-1α in the regulation of the above UGTs. Methods Liver samples (n=83) were genotyped for HNF-1α 79A>C and for UGT variants affecting their expression. HNF-1α and UGT mRNA levels were measured by real time PCR. Results No correlation was observed between HNF-1α expression and that of UGT1A1, UGT1A9 and UGT2B7 (r2=0.0002, p>0.05; r2=0.09, p=0.02; r2=0.04, p>0.05, respectively; log transformed). HNF-1α genotypes were not associated with UGT mRNA levels (p>0.05). Significant correlations were found between UGT1A1 expression and the *28 polymorphism (6/6>6/7>7/7, p=0.03, nonparametric trend), UGT1A9 expression and the *22 T indel polymorphism (9/9+9/10 vs. 10/10, p=0.02, Mann-Whitney), and UGT2B7 expression and an intronic gene variant (A/A vs. A/G+G/G; p=0.01, Mann-Whitney). HNF-1α genotypes seemed not to predict UGT mRNA levels in multivariate analysis. Conclusion Our data do not provide evidence of a significant role of HNF-1α in the prediction of interindividual variability in UGT1A1, UGT1A9 and UGT2B7 expression. Variation in cis-acting regulatory UGT elements might have a stronger phenotypic effect. Clinical Pharmacology & Therapeutics (2005) 77, P61–P61; doi: 10.1016/j.clpt.2004.12.125