English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Zendy Open

Presents the pdf analysis as premium feature

PDF Analysis

Insights

Presents the summarisation as premium feature

Summarisation

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the zaia usage as premium feature

ZAIA

Zendy Tools

Zendy Plus

Presents the access of premium content as premium feature

Premium Content

The aim of this study was to discover  cis - and  trans -acting factors significantly affecting mRNA expression and catalytic activity of human hepatic UDP-glucuronosyltransferases (UGTs). Transcription levels of five major hepatic  UGT1A  ( UGT1A1, UGT1A3, UGT1A4, UGT1A6  and  UGT1A9 ) and five  UGT2B  ( UGT2B4, UGT2B7, UGT2B10, UGT2B15  and  UGT2B17 ) genes were quantified in human liver tissue samples ( n  = 125) using real-time PCR. Glucuronidation activities of 14 substrates were measured in 47 livers. We genotyped 167 tagSNPs (single-nucleotide polymorphisms) in  UGT1A  ( n  = 43) and  UGT2B  ( n  = 124), as well as the known functional  UGT1A1*28  and  UGT2B17  CNV (copy number variation) polymorphisms. Transcription levels of 15 transcription factors (TFs) known to regulate these  UGTs  were quantified. We found that  UGT  expression and activity were highly variable among the livers (median and range of coefficient of variations: 135%, 74–217% and 52%, 39–105%, respectively). CAR, PXR and ESR1 were found to be the most important  trans -regulators of UGT transcription (median and range of correlation coefficients: 46%, 6–58%; 47%, 9–58%; and 52%, 24–75%, respectively). Hepatic UGT activities were mainly determined by  UGT  gene transcription levels. Twenty-one polymorphisms were significantly (FDR-adjusted  P  &lt; 0.05) associated with mRNA expression and/or activities of  UGT1A1 ,  UGT1A3  and  UGT2B17 . We found novel SNPs in the  UGT2B17  CNV region accounting for variability in  UGT2B17  gene transcription and testosterone glucuronidation rate, in addition to that attributable to the  UGT2B17  CNV. Our study discovered novel pharmacogenetic markers and provided detailed insight into the genetic network regulating hepatic UGTs.

Genetic factors affecting gene transcription and catalytic activity of UDP-glucuronosyltransferases in human liver