Evidence map›Paper›PMID 30538005›Full record

ArticleCritical care (London, England)2018

Evidence for a protective role for the rs805305 single nucleotide polymorphism of dimethylarginine dimethylaminohydrolase 2 (DDAH2) in septic shock through the regulation of DDAH activity.

Simon Lambden, James Tomlinson, Sophie Piper, Anthony C Gordon, James Leiper

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

Article in Critical care (London, England), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.7field-weighted citation impact, top 29% 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

7 citing papers in PubMed, 13 citations in OpenAlex.

  1. Article
  2. Article
  3. Early and late-onset preeclampsia: effects of DDAH2 polymorphisms on ADMA levels and association with DDAH2 haplotypes.Revista brasileira de ginecologia e obstetricia : revista da Federacao Brasileira das Sociedades de Ginecologia e Obstetricia · 2024
    Article
  4. Article
  5. Review
  6. Article
  7. 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

5 authors at 4 institutions in 1 country.

Simon LambdenDepartment of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge, CB2OQQ, UK.
James TomlinsonMRC London Institute of Medical Sciences, Hammersmith Hospital Campus, Du Cane Road, London, W12 0NN, UK.
Sophie PiperMRC London Institute of Medical Sciences, Hammersmith Hospital Campus, Du Cane Road, London, W12 0NN, UK.
Anthony C GordonSection of Anaesthetics, Pain Medicine and Intensive Care, Faculty of Medicine, Imperial College London, London, UK.
James LeiperInstitute of Cardiovascular and Medical Sciences, University of Glasgow, University Avenue, Glasgow, G12 8QQ, UK. James.Leiper@glasgow.ac.uk.
Hammersmith Hospital · GBAddenbrooke's Hospital · GBImperial College London · GBMRC London Institute of Medical Sciences · GB

Funding

Department of Health NIHR/CS/009/007Research for Patient Benefit Programme PB-PG-0610-22350
6 · The paper itself

Abstract

backgroundDimethylarginine dimethylaminohydrolase 2 (DDAH2) regulates the synthesis of nitric oxide (NO) through the metabolism of the endogenous inhibitor of nitric oxide synthase, asymmetric dimethylarginine (ADMA). Pilot studies have associated the rs805305 SNP of DDAH2 with ADMA concentrations in sepsis. This study explored the impact of the rs805305 polymorphism on DDAH activity and outcome in septic shock.

methodsWe undertook a secondary analysis of data and samples collected during the Vasopressin versus noradrenaline as initial therapy in septic shock (VANISH) trial. Plasma and DNA samples isolated from 286 patients recruited into the VANISH trial were analysed. Concentrations of L-Arginine and the methylarginines ADMA and symmetric dimethylarginine (SDMA) were determined from plasma samples. Whole blood and buffy-coat samples were genotyped for polymorphisms of DDAH2. Clinical data collected during the study were used to explore the relationship between circulating methylarginines, genotype and outcome.

resultsPeak ADMA concentration over the study period was associated with a hazard ratio for death at 28 days of 3.3 (95% CI 2.0-5.4), p < 0.001. Reduced DDAH activity measured by an elevated ADMA:SDMA ratio was associated with a reduced risk of death in septic shock (p = 0.03). The rs805305 polymorphism of DDAH2 was associated with reduced DDAH activity (p = 0.004) and 28-day mortality (p = 0.02). Mean SOFA score and shock duration were also reduced in the less common G:G genotype compared to heterozygotes and C:C genotype patients (p = 0.04 and p = 0.02, respectively).

conclusionsPlasma ADMA is a biomarker of outcome in septic shock, and reduced DDAH activity is associated with a protective effect. The polymorphism rs805305 SNP is associated with reduced mortality, which is potentially mediated by reduced DDAH2 activity.

trial registrationISRCTN Registry, ISRCTN20769191 . Registered on 20 September 2012.

Indexed as

AmidohydrolasesArginineBiomarkersHumansOrgan Dysfunction ScoresPolymorphism, Single NucleotideProtective AgentsShock, SepticStatistics, NonparametricTime FactorsAmidohydrolasesArginineBiomarkersdimethylargininaseN,N-dimethylarginineProtective Agentssymmetric dimethylarginineClinical studiesGeneticsMortality/survivalNitric oxideNitric oxide synthaseSepsisSeptic shockTranslational studies

Identifiers

PMID30538005
PMCPMC6288902
OpenAlexW2905287798

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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.