Evidence map›Paper›PMID 33649974›Full record

ArticleThe AAPS journal2021

The Effects of Genetic Mutations and Drugs on the Activity of the Thiamine Transporter, SLC19A2.

Osatohanmwen J Enogieru, Megan L Koleske, Bianca Vora, Huy Ngo, Sook Wah Yee, Derrick Chatad, Marina Sirota, Kathleen M Giacomini

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The AAPS journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.3field-weighted citation impact, top 40% 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

1 citing paper in PubMed, 3 citations in OpenAlex.

  1. 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

8 authors at 2 institutions in 1 country.

Osatohanmwen J EnogieruDepartment of Bioengineering and Therapeutic Sciences, University of California at San Francisco, San Francisco, California, 94158, USA.
Megan L KoleskeDepartment of Bioengineering and Therapeutic Sciences, University of California at San Francisco, San Francisco, California, 94158, USA.
Bianca VoraDepartment of Bioengineering and Therapeutic Sciences, University of California at San Francisco, San Francisco, California, 94158, USA.
Huy NgoDepartment of Bioengineering and Therapeutic Sciences, University of California at San Francisco, San Francisco, California, 94158, USA.
Sook Wah YeeDepartment of Bioengineering and Therapeutic Sciences, University of California at San Francisco, San Francisco, California, 94158, USA.
Derrick ChatadCollege of Medicine, SUNY Downstate Health Sciences University, Brooklyn, New York, 11203, USA.
Marina SirotaDepartment of Pediatrics, University of California at San Francisco, San Francisco, California, 94158, USA.
Kathleen M GiacominiDepartment of Bioengineering and Therapeutic Sciences, University of California at San Francisco, San Francisco, California, 94158, USA. kathy.giacomini@ucsf.edu.
University of California, San Francisco · USSUNY Downstate Health Sciences University · US

Funding

Clinical and Translational Science InstituteUL1TR001872 · NCATS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI COLLARD, HAROLD R, JACOBY, VANESSA · 2016 to 2025
$112.1M
ZIDOVUDINE &LAMIVUDINE &NEVIRAPINE COMBINATION THERAPY IN HIV 1 INFM01RR001271 · NCRR · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KESSLER, DAVID A · 1985 to 2006
$22.7M
Research BaseP30DK063720 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KRUMMEL, MATTHEW F · 2003 to 2019
$21.8M
UCSF Nutrition Obesity Research CenterP30DK098722 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHRISTIAN VAISSE · 2015 to 2026
$14.6M
SF BUILD: Enabling Students to Represent in ScienceTL4GM118986 · NIGMS · SAN FRANCISCO STATE UNIVERSITY · PI MARQUEZ-MAGANA, LETICIA MARIA, MORRIS, MEGHAN D · 2015 to 2022
$5.4M
Drug-Vitamin Interactions Mediated by the Thiamine Transporter, SLC19A3R01DK108722 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GIACOMINI, KATHLEEN M, GREENBERG, ANDREW S · 2017 to 2020
$2.6M
NCATS NIH HHS UL1 TR001872NCRR NIH HHS M01 RR001271NIDDK NIH HHS P30 DK063720NIDDK NIH HHS P30 DK098722NIDDK NIH HHS R01 DK108722NIGMS NIH HHS TL4 GM118986
6 · The paper itself

Abstract

A rare cause of megaloblastic anemia (MA) is thiamine-responsive megaloblastic anemia (TRMA), a genetic disorder caused by mutations in SLC19A2 (encoding THTR1), a thiamine transporter. The study objectives were to (1) functionally characterize selected TRMA-associated SLC19A2 variants and (2) determine whether current prescription drugs associated with drug-induced MA (DIMA) may act via inhibition of SLC19A2. Functional characterization of selected SLC19A2 variants was performed by confocal microscopy and isotopic uptake studies of [3H]-thiamine in HEK293 cells. Sixty-three drugs associated with DIMA were screened for SLC19A2 inhibition in isotopic uptake studies. Three previously uncharacterized SLC19A2 variants identified in TRMA patients exhibited disrupted localization to the plasma membrane along with near-complete loss-of-function. Ten of 63 drugs inhibited SLC19A2-mediated thiamine transport ≥ 50% at screening concentrations; however, with the exception of erythromycin, none was predicted to inhibit SLC19A2 at clinically relevant unbound plasma concentrations. Data from electronic health records revealed reduced levels of thiamine pyrophosphate (TPP) in patients prescribed erythromycin, consistent with inhibition of SLC19A2-mediated thiamine transport. Here, we confirmed the role of three SLC19A2 variants in TRMA pathology. Additionally, we report that inhibition of SLC19A2 is a potential, but uncommon mechanism for DIMA.

Indexed as

AdultAnemia, MegaloblasticCell MembraneDiabetes MellitusDrug InteractionsErythromycinFemaleGenetic VariationHearing Loss, SensorineuralHEK293 CellsHumansLoss of Function MutationMaleMembrane Transport ProteinsThiamine DeficiencyThiamine PyrophosphateErythromycinMembrane Transport ProteinsSLC19A2 protein, humanThiamine Pyrophosphatedrug-induced megaloblastic anemiadrug nutrient interactionsthiamine diphosphateTHTR1vitamin b1

Identifiers

PMID33649974
PMCPMC7921063
OpenAlexW3133962070

What OpenQuestion holds

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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.