Evidence map›Paper›PMID 22661630›Full record

ArticleThe Journal of pharmacology and experimental therapeutics2012

Quantification of Hepatic UDP glucuronosyltransferase 1A splice variant expression and correlation of UDP glucuronosyltransferase 1A1 variant expression with glucuronidation activity.

Nathan R Jones, Dongxiao Sun, Willard M Freeman, Philip Lazarus

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of pharmacology and experimental therapeutics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
6.0field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 27 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Frontiers in genetics · 2020
    Article
  5. Article
  6. Article
  7. Review
  8. UGT2B gene expression analysis in multiple tobacco carcinogen-targeted tissues.Drug metabolism and disposition: the biological fate of chemicals · 2014
    Article
  9. Regulation of UDP-glucuronosyltransferase 1A1 expression and activity by microRNA 491-3p.The Journal of pharmacology and experimental therapeutics · 2014
    Article
  10. Article
  11. Article
  12. Importance of UDP-glucuronosyltransferases 2A2 and 2A3 in tobacco carcinogen metabolism.Drug metabolism and disposition: the biological fate of chemicals · 2013
    Article
  13. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

Nathan R JonesDepartment of Pharmacology, Pennsylvania State College of Medicine, Hershey, Pennsylvania, USA.
Dongxiao Sun
Willard M Freeman
Philip Lazarus
Penn State Milton S. Hershey Medical Center · US

Funding

UDPGLUCURONOSYLTRANSFERASE GENOTYPE AND ORAL CANCER RISKR01DE013158 · NIDCR · UNIVERSITY OF SOUTH FLORIDA · PI LAZARUS, PHILIP · 2000 to 2011
$3.6M
NIDCR NIH HHS R01 DE013158NIDCR NIH HHS R01-DE13158
6 · The paper itself

Abstract

The UDP glucuronosyltransferase (UGT) 1A gene cluster encodes nine UGT1A family members via splicing of individual first exons to common exons 2 through 5. Each of these nine UGT1As can also undergo alternative splicing at their 3' ends by using an alternate exon 5, resulting in 27 different UGT1A mRNA species with each UGT1A gene encoding three different combinations of 5A and 5B UGT1A exons. To examine the importance of UGT1A exon 5 splice variants on overall UGT1A activity, a nested quantitative polymerase chain reaction assay was developed to accurately assess the combined expression of exon 5 splice variants (termed v2/v3) versus the expression of wild-type (termed v1) for each specific UGT1A. v1 expression was 16-, 17-, 57- and 29-fold higher than that observed for the levels of v2/v3 for UGTs 1A1, 1A4, 1A6, and 1A9, respectively, in normal human liver specimens. In a series of 58 normal human liver specimens, the expression of both UGT1A1 v1 and v2/v3 mRNAs was positively correlated with raloxifene glucuronidation activity in corresponding microsomes prepared from the same specimens (p < 0.0001, r² = 0.720; p = 0.0002, r² = 0.241, respectively), with expression of both variants lower in individuals homozygous for the UGT1A1*28 allele (42% for v1, p = 0.041; 53% for v2/v3, p = 0.0075). The expression of UGT1A1 v2/v3 was 1.6-fold higher than v1 (p = 0.03) in HepG2 cells, and short interfering RNA knockdown of HepG2 v2/v3 increased raloxifene glucuronidation activity by 83%. Together, these data suggest that hepatic UGT1A v2/v3 mRNA species are minor form variants in human livers from most individuals.

Indexed as

Alternative SplicingCell LineCell Line, TumorExonsGene Knockdown TechniquesGlucuronosyltransferaseHep G2 CellsHumansLiverMicrosomes, LiverRaloxifene HydrochlorideRNA, MessengerRNA, Small InterferingUGT1A1 EnzymeGlucuronosyltransferaseRaloxifene HydrochlorideRNA, MessengerRNA, Small InterferingUGT1A1 Enzyme

Identifiers

PMID22661630
PMCPMC3422519
OpenAlexW2097079942

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.