Evidence map›Paper›PMID 36148820›Full record

SynthesisEuropean journal of neurology2023

Genetic variation in NFE2L2 is associated with outcome following aneurysmal subarachnoid haemorrhage.

Ben Gaastra, Poppy Duncan, Mark K Bakker, Isabel C Hostettler, Varinder S Alg, Henry Houlden, Ynte M Ruigrok, Ian Galea, Will Tapper, David Werring and 1 more

Open access · hybridAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in European journal of neurology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 1 pooled it
1.1field-weighted citation impact, top 20% 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, 1 synthesis or guideline pooled it, 8 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Article
  4. Review
  5. Review
  6. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 5 institutions in 3 countries.

Ben GaastraClinical Neurosciences, Clinical & Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.ORCID 0000-0002-7517-6882
Poppy DuncanClinical Neurosciences, Clinical & Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.
Mark K BakkerDepartment of Neurology, University Medical Center Utrecht Brain Center, University Medical Center Utrecht, Utrecht, the Netherlands.
Isabel C HostettlerStroke Research Centre, University College London, Institute of Neurology, London, UK.
Varinder S AlgStroke Research Centre, University College London, Institute of Neurology, London, UK.
Henry HouldenStroke Research Centre, University College London, Institute of Neurology, London, UK.
Ynte M RuigrokDepartment of Neurology, University Medical Center Utrecht Brain Center, University Medical Center Utrecht, Utrecht, the Netherlands.
Ian GaleaClinical Neurosciences, Clinical & Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.ORCID 0000-0002-1268-5102
Will TapperClinical Neurosciences, Clinical & Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.
David WerringStroke Research Centre, University College London, Institute of Neurology, London, UK.
Diederik BultersDepartment of Neurosurgery, Wessex Neurological Centre, University Hospital Southampton, Southampton, UK.
Stroke Association · GBUniversity of Southampton · GBUniversity Hospital Southampton NHS Foundation Trust · GBUniversity Medical Center Utrecht · NLKantonsspital St. Gallen · CH

Funding

Medical Research Council MR/S01165X/1
6 · The paper itself

Abstract

background and purposeNuclear factor erythroid 2-related factor 2 (NRF2; encoded by the NFE2L2 gene) has been implicated in outcome following aneurysmal subarachnoid haemorrhage (aSAH) through its activity as a regulator of inflammation, oxidative injury and blood breakdown product clearance. The aim of this study was to identify whether genetic variation in NFE2L2 is associated with clinical outcome following aSAH.

methodsTen tagging single nucleotide polymorphisms (SNPs) in NFE2L2 were genotyped and tested for association with dichotomized clinical outcome, assessed by the modified Rankin scale, in both a discovery and a validation cohort. In silico functional analysis was performed using a range of bioinformatic tools.

resultsOne SNP, rs10183914, was significantly associated with outcome following aSAH in both the discovery (n = 1007) and validation cohorts (n = 466). The risk of poor outcome was estimated to be 1.33-fold (95% confidence interval 1.12-1.58) higher in individuals with the T allele of rs10183914 (p

conclusionsThe NFE2L2 SNP, rs10183914, is significantly associated with outcome following aSAH. This is consistent with a clinically relevant pathophysiological role for oxidative and inflammatory brain injury due to blood and its breakdown products in aSAH. Furthermore, our findings support NRF2 as a potential therapeutic target following aSAH and other forms of intracranial haemorrhage.

Indexed as

Subarachnoid HemorrhageAllelesGenotypeHumansNF-E2-Related Factor 2Polymorphism, Single NucleotideNFE2L2 protein, humanNF-E2-Related Factor 2NF-E2-related factor 2polymorphism, single nucleotidesubarachnoid haemorrhage

Identifiers

PMID36148820
PMCPMC10092511
OpenAlexW4296807754

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.