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

J. Ramírez; S. Mirkov; W. Zhang; P. Chen; S. Das; W. Liu; M. J. Ratain; F. Innocenti

doi:10.1038/sj.tpj.6500454

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

J. Ramírez, S. Mirkov, W. Zhang, P. Chen, S. Das, W. Liu, M. J. Ratain, F. Innocenti^*

^*Corresponding author for this work

Preventive Medicine

Research output: Contribution to journal › Article › peer-review

27 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	152-161
Number of pages	10
Journal	Pharmacogenomics Journal
Volume	8
Issue number	2
DOIs	https://doi.org/10.1038/sj.tpj.6500454
State	Published - Apr 2008

Funding

We thank James Chandler for assistance in genotyping HNF1a 79A>C. This work was supported by the Pharmacogenetics of Anticancer Agents Research (PAAR) Group (http://pharmacogenetics. org) (NIH/NIGMS grant U01GM61393). Data will be deposited into PharmGKB (supported by NIH/NIGMS U01GM61374, http:// pharmgkb.org/).

ASJC Scopus subject areas

Genetics
Molecular Medicine
Pharmacology

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

abstract = "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.",

author = "J. Ram{\'i}rez and S. Mirkov and W. Zhang and P. Chen and S. Das and W. Liu and Ratain, {M. J.} and F. Innocenti",

note = "Funding Information: We thank James Chandler for assistance in genotyping HNF1a 79A>C. This work was supported by the Pharmacogenetics of Anticancer Agents Research (PAAR) Group (http://pharmacogenetics. org) (NIH/NIGMS grant U01GM61393). Data will be deposited into PharmGKB (supported by NIH/NIGMS U01GM61374, http:// pharmgkb.org/).",

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AU - Chen, P.

AU - Das, S.

AU - Liu, W.

AU - Ratain, M. J.

AU - Innocenti, F.

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N2 - 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.

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

Abstract

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