Evidence map›Paper›PMID 35671649›Full record

Trial reportSeminars in arthritis and rheumatism2022

Genetics are not likely to offer clinically useful predictions for elevated liver enzyme levels in patients using low dose methotrexate.

Jing Cui, Daniel I Chasman, Soumya Raychaudhuri, Chang Xu, Paul M Ridker, Daniel H Solomon, Elizabeth W Karlson

Open access · greenAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Seminars in arthritis and rheumatism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed, 1 pooled it
0.2field-weighted citation impact, top 50% 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, 1 synthesis or guideline pooled it, 1 citations in OpenAlex.

  1. Pooled it
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

7 authors at 1 institution in 1 country.

Jing CuiDivision of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital USA. Electronic address: jcui@bwh.harvard.edu.
Daniel I ChasmanDivision of Preventive Medicine, Brigham and Women's Hospital USA; Division of Genetics, Brigham and Women's Hospital, Boston, MA USA.
Soumya RaychaudhuriDivision of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital USA; Division of Genetics, Brigham and Women's Hospital, Boston, MA USA.
Chang XuDivision of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital USA.
Paul M RidkerDivision of Preventive Medicine, Brigham and Women's Hospital USA.
Daniel H SolomonDivision of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital USA.
Elizabeth W KarlsonDivision of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital USA.
Brigham and Women's Hospital · US

Funding

Cardiovascular Inflammation Reduction Trial (CIRT)U01HL101422 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI RIDKER, PAUL M. · 2011 to 2018
$55.4M
Joint Biology Consortium Resource-based CenterP30AR070253 · NIAMS · BRIGHAM AND WOMEN'S HOSPITAL · PI Peter A Nigrovic, Jeffrey Andrew Sparks · 2016 to 2026
$9.4M
Cardiovascular Inflammation Reduction Trial (CIRT): DCCU01HL101389 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI GLYNN, ROBERT J · 2011 to 2016
$6.6M
Discovery and Functional Impact of Common and Rare Variants in RAR01AR063759 · NIAMS · BRIGHAM AND WOMEN'S HOSPITAL · PI Soumya Raychaudhuri · 2013 to 2026
$5.4M
Towards Evidence-Based Monitoring of Low Dose Methotrexate: CIRT Ancillary StudyR01HL119718 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI SOLOMON, DANIEL HAL · 2014 to 2018
$3.9M
NHLBI NIH HHS R01 HL119718NHLBI NIH HHS U01 HL101389NHLBI NIH HHS U01 HL101422NIAMS NIH HHS P30 AR070253NIAMS NIH HHS R01 AR063759
6 · The paper itself

Abstract

objectiveTo examine genetic influence on the risk of elevations in liver function tests (AST and ALT) among patients using low-dose methotrexate (LD-MTX).

methodsWe examined data from the LD-MTX arm of a randomized double-blind placebo-controlled trial conducted among subjects without rheumatic disease. Genome wide association studies (GWAS) were performed in subjects of European ancestry to test the association between single nucleotide polymorphisms (SNPs) and the log transformed maximum values of AST, ALT, and dichotomized outcome with AST or ALT > 2 times upper limit of normal (ULN). The association between variants in MTX metabolism candidate genes and the outcomes was also tested. Furthermore, associations between a drug induced liver injury (DILI) weighted genetic risk score (wGRS) and the outcomes were tested, combining 10 SNPs and 11 classical HLA alleles associated with DILI.

resultsIn genome-wide genetic analyses among 1,429 subjects of European ancestry who were randomized to receive LD-MTX, two SNPs reached genome wide significance for association with log transformed maximum ALT. We observed associations between established candidate genes in MTX pharmacogenetics and log transformed maximum AST and ALT, as well as in dichotomized outcome with AST or ALT > 2 x ULN. There was no association between DILI wGRS or candidate variants and AST, ALT, or DILI response.

conclusionsModest evidence was observed that common variants affected AST and ALT levels in subjects of European ancestry on LD-MTX, but this genetic effect is not useful as a clinical predictor of MTX toxicity.

Indexed as

Chemical and Drug Induced Liver InjuryMethotrexateGenome-Wide Association StudyHumansRisk FactorsMethotrexateDrug induced liver injuryGenetic risk scoreGenome wide association studyLow dose methotrexatePharmacogenetics

Identifiers

PMID35671649
PMCPMC10782828
OpenAlexW4281736099

What OpenQuestion holds

Textmetadata
LicenceTDM
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.