Evidence map›Paper›PMID 29579042›Full record

Trial reportPloS one2018

Genetic variants in cellular transport do not affect mesalamine response in ulcerative colitis.

Christopher J Moran, Hailiang Huang, Manuel Rivas, Jess L Kaplan, Mark J Daly, Harland S Winter

Open access · goldAbstract readClinical Trial, Phase IIIRandomized Controlled Trial
In one paragraph

Trial report in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.6field-weighted citation impact, top 30% 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

6 citing papers in PubMed, 11 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
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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 2 institutions in 1 country.

Christopher J MoranDivision of Pediatric Gastroenterology, Hepatology, & Nutrition, MassGeneral Hospital for Children, Boston, Massachusetts, United States of America.ORCID 0000-0003-1966-3499
Hailiang HuangAnalytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, United States of America.
Manuel RivasAnalytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, United States of America.
Jess L KaplanDivision of Pediatric Gastroenterology, Hepatology, & Nutrition, MassGeneral Hospital for Children, Boston, Massachusetts, United States of America.
Mark J DalyAnalytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, United States of America.
Harland S WinterDivision of Pediatric Gastroenterology, Hepatology, & Nutrition, MassGeneral Hospital for Children, Boston, Massachusetts, United States of America.
Broad Institute · USHarvard University · US

Funding

Pilot & Feasibility ProgramP30DK043351 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI Ramnik J Xavier · 1991 to 2026
$35.3M
Genetics and gene regulation in the inflammatory bowel diseasesK01DK114379 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI HUANG, HAILIANG · 2017 to 2021
$632k
NIDDK NIH HHS K01 DK114379NIDDK NIH HHS P30 DK043351
6 · The paper itself

Abstract

BACKGROUND AND

aimsMesalamine is commonly used to treat ulcerative colitis (UC). Although mesalamine acts topically, in vitro data suggest that intracellular transport is required for its beneficial effect. Genetic variants in mucosal transport proteins may affect this uptake, but the clinical relevance of these variants has not been studied. The aim of this study was to determine whether variants in genes involved in cellular transport affect the response to mesalamine in UC.

methodsSubjects with UC from a 6-week clinical trial using multiple doses of mesalamine were genotyped using a genome-wide array that included common exome variants. Analysis focused on cellular transport gene variants with a minor allele frequency >5%. Mesalamine response was defined as improvement in Week 6 Physician's Global Assessment (PGA) and non-response as a lack of improvement in Week 6 PGA. Quality control thresholds included an individual genotyping rate of >90%, SNP genotyping rate of >98%, and exclusion for subjects with cryptic relatedness. All included variants met Hardy-Weinberg equilibrium (p>0.001).

results457 adults with UC were included with 280 responders and 177 non-responders. There were no common variants in transporter genes that were associated with response to mesalamine. The genetic risk score of responders was similar to that of non-responders (p = 0.18). Genome-wide variants demonstrating a trend towards mesalamine response included ST8SIA5 (p = 1x10-5).

conclusionsCommon transporter gene variants did not affect response to mesalamine in adult UC. The response to mesalamine may be due to rare genetic events or environmental factors such as the intestinal microbiome.

Indexed as

Colitis, UlcerativeMesalaminePolymorphism, Single NucleotideAdultBiological Transport, ActiveFemaleHumansMaleMiddle AgedPharmacogenomic TestingSialyltransferasesMesalamineSialyltransferasesST8SIA5 protein, human

Identifiers

PMID29579042
PMCPMC5868763
OpenAlexW2792100977

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.