Evidence map›Paper›PMID 24548980›Full record

ArticleInternational journal of clinical pharmacology and therapeutics2014

A pilot study of leukocyte expression patterns for drug metabolizing enzyme and transporter transcripts in autoimmune glomerulonephritis.

Melanie S Joy, Brittney V Roberts, Jinzhao Wang, Yichun Hu, Susan L Hogan, Ronald J Falk

Open access · greenAbstract read
In one paragraph

Article in International journal of clinical pharmacology and therapeutics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.3field-weighted citation impact, top 37% 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

3 citing papers in PubMed, 10 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
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

6 authors at 1 institution in 1 country.

Melanie S Joy
Brittney V Roberts
Jinzhao Wang
Yichun Hu
Susan L Hogan
Ronald J Falk
University of Montana · US

Funding

Zonisamide in Patients with Neuropathic Pain Associated with Diabetic NeuropathyM01RR000046 · NCRR · UNIV OF NORTH CAROLINA CHAPEL HILL · PI JOY, MELANIE S · 1985 to 2008
$38.5M
Translation of Knowledge on the Pathogenesis of ANCA Disease into NovelP01DK058335 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI JENNETTE, CHARLES · 2000 to 2019
$25.9M
Pharmacokinetics &Genomics in Glomerular DiseasesK23DK064888 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI JOY, MELANIE S · 2004 to 2008
$609k
NCRR NIH HHS RR00046NCRR NIH HHS U54RR024383NIDDK NIH HHS 5K23DK64888NIDDK NIH HHS P01 DK058335
6 · The paper itself

Abstract

objectiveLeukocyte mRNA expression patterns of drug metabolizing enzyme genes and transporter genes that are relevant for the disposition of cyclophosphamide and mycophenolate were studied. The relationships between expression and patient-level data and pharmacokinetics were evaluated.

methodsThe study included patients with glomerulonephritis secondary to lupus nephritis (SLE, n = 36), small vessel vasculitis (SVV, n = 35), healthy controls (HC, n = 10), and disease controls (VC, n = 5; LC, n = 5). Transcript assays targeted metabolizing enzymes (UGT1A7, UGT1A9, UGT2B7, CYP3A4, CYP2C9, CYP2B6) and transporters (ABCB1, ABCC2, ABCG2, SLCO1A2). Genotyping for specific variants was conducted. Group transcript fold-changes were evaluated. Patient level data was evaluated for transcript foldchange and disease, treatment, gender, race, and genotype.

resultsSignificant differences were noted in expression of UGT1A7, ABCB1, and ABCC2; for UGT1A7, SVV (0.17 ± 0.42; p < 0.05) and SLE (0.03 ± 0.1; p < 0.05) groups had lower expression than HC (0.79 ± 2.02). For ABCB1, SLE had a lower expression (0.33 ± 0.21; p < 0.05) than HCs (1 ± 0.82). For ABCG2, SVV group had a lower expression (0.17 ± 0.14; p < 0.05) than HCs (1 ± 1.82). Differences in expression of ABCC2 approached statistical significance with VC patients (2.02 ± 1.13) exhibiting higher expression than SVV patients (1.06 ± 1.11; p = 0.05). The relationships between transcript expression and patient-level data demonstrated; ABCC2 expression was different by race (1.26 ± 1.82 Caucasian versus 1.37 ± 0.86 non-Caucasian; p = 0.049) and CYP2B6 expression was different by treatment (2.07 ± 2.94 cyclophosphamide versus 0.45 ± 0.5 mycophenolate; p = 0.01).

conclusionsThe current study showed differential expression of drug metabolizing enzyme and transporter transcripts and contributes to the literature on transcript expression of drug transporters in leukocytes. The implications of altered local metabolism and transport in leukocytes may be important in autoimmune diseases and transplant patients where treatment is targeted to leukocytes.

Indexed as

ATP-Binding Cassette, Sub-Family C ProteinsATP Binding Cassette Transporter, Subfamily BATP Binding Cassette Transporter, Subfamily B, Member 1Autoimmune DiseasesCyclophosphamideGenotypeGlomerulonephritisHumansLeukocytesMultidrug Resistance-Associated Protein 2Mycophenolic AcidPilot ProjectsRNA, MessengerABCB1 protein, humanABCC2 protein, humanATP-Binding Cassette, Sub-Family C ProteinsATP Binding Cassette Transporter, Subfamily BATP Binding Cassette Transporter, Subfamily B, Member 1CyclophosphamideMultidrug Resistance-Associated Protein 2Mycophenolic AcidRNA, Messenger

Identifiers

PMID24548980
PMCPMC4123858
OpenAlexW2320651441

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.