Evidence map›Paper›PMID 30277801›Full record

ArticleDNA and cell biology2018

Promoter Haplotypes of the ABCB1 Gene Encoding the P-Glycoprotein Differentially Affect Its Promoter Activity by Altering Transcription Factor Binding.

Jordan T Speidel, Meixiang Xu, Sherif Z Abdel-Rahman

Abstract read
In one paragraph

Article in DNA and cell biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. Regulation of P-Glycoprotein during Oxidative Stress.Antioxidants (Basel, Switzerland) · 2024
    Review
  3. Article
  4. A T > G Mutation in theFrontiers in genetics · 2019
    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

3 authors at 1 institution in 1 country.

Jordan T Speidel1 Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch at Galveston, Galveston, Texas.
Meixiang Xu2 Maternal-Fetal Pharmacology and Biodevelopment Laboratories, Department of Obstetrics and Gynecology, The University of Texas Medical Branch at Galveston, Galveston, Texas.
Sherif Z Abdel-Rahman2 Maternal-Fetal Pharmacology and Biodevelopment Laboratories, Department of Obstetrics and Gynecology, The University of Texas Medical Branch at Galveston, Galveston, Texas.
The University of Texas Medical Branch at Galveston · US

Funding

Synthetic Organic Chemistry CoreP30ES006676 · NIEHS · UNIVERSITY OF TEXAS MEDICAL BR GALVESTON · PI ELFERINK, CORNELIS JOHAN · 1995 to 2017
$21.7M
UTMB Clinical and Translational Science AwardUL1TR000071 · NCATS · UNIVERSITY OF TEXAS MED BR GALVESTON · PI BRASIER, ALLAN R. · 2012 to 2014
$14.4M
Molecular Mechanisms of Environmental InjuryT32ES007254 · NIEHS · UNIVERSITY OF TEXAS MEDICAL BR GALVESTON · PI AMEREDES, BILL T · 1990 to 2022
$6.6M
UTMB OPRC Administrative CoreU54HD047891 · NICHD · UNIVERSITY OF TEXAS MED BR GALVESTON · PI CLARK, SHANNON MICHELLE · 2015 to 2019
$4.8M
Bupropion for smoking cessation during pregnancyR01DA030998 · NIDA · UNIVERSITY OF TEXAS MED BR GALVESTON · PI HANKINS, GARY D, NANOVSKAYA, TATIANA · 2010 to 2015
$4.1M
NCATS NIH HHS UL1 TR000071NICHD NIH HHS U54 HD047891NIDA NIH HHS R01 DA030998NIEHS NIH HHS P30 ES006676NIEHS NIH HHS T32 ES007254
6 · The paper itself

Abstract

Promoter single nucleotide polymorphisms (SNPs) of the ABCB1 gene, encoding the placental efflux transporter P-glycoprotein, can alter its expression and affect fetal exposure to therapeutics and environmental xenobiotics. SNPs are not arrayed as independent variants but as combinations forming defined haplotypes. Recently, we defined the haplotypes encompassing ABCB1 promoter SNPs and found that ABCB1 haplotypes differentially affect its promoter activity. The mechanism(s) by which ABCB1 haplotypes alter its promoter activity are not known. We hypothesize that the haplotype-dependent differences in ABCB1 promoter activity are due to haplotype-specific alterations in transcription factor (TF) binding. To test our hypothesis, we used a TF binding profile array and determined whether differences in TF binding exist across different ABCB1 haplotypes. TFs showing significant haplotype binding differences were mechanistically evaluated using small interfering RNA (siRNA) in cultured human placental cells. Our data indicate significant haplotype-dependent differences in TF binding. Our siRNA studies showed that the regulatory effects of TFs on promoter activity are also haplotype dependent. Our data provide a mechanistic explanation for the differential effects of ABCB1 haplotypes on its promoter activity and underscore the importance of evaluating genetic variants in the context of haplotypes rather than individual SNPs when investigating their effects on gene/protein expression and disease risk.

Indexed as

ATP Binding Cassette Transporter, Subfamily BATP Binding Cassette Transporter, Subfamily B, Member 1Cell LineGenetic VariationHaplotypesHumansPolymorphism, Single NucleotidePromoter Regions, GeneticProtein BindingTranscription FactorsTranscription, GeneticABCB1 protein, humanATP Binding Cassette Transporter, Subfamily BATP Binding Cassette Transporter, Subfamily B, Member 1Transcription FactorsexpressionhaplotypesP-glycoproteinSNPstranscription factors

Identifiers

PMID30277801
PMCPMC6302815
OpenAlexW2894841081

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.