Evidence map›Paper›PMID 37415141›Full record

ArticleRespiratory research2023

Xanthine oxidoreductase gene polymorphisms are associated with high risk of sepsis and organ failure.

Li Gao, Nicholas Rafaels, Tanda M Dudenkov, Mahendra Damarla, Rachel Damico, James P Maloney, Marc Moss, Greg S Martin, Jonathan Sevransky, Carl Shanholtz and 9 more

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

Article in Respiratory research, 2023. 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
1.5field-weighted citation impact, top 18% 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, 8 citations in OpenAlex.

  1. Review
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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

19 authors at 8 institutions in 4 countries.

Li GaoDepartment of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. lgao2@jhmi.edu.
Nicholas RafaelsDivision of Biomedical Informatics & Personalized Medicine, University of Colorado School of Medicine, Aurora, CO, USA.
Tanda M DudenkovDepartment of Epidemiology, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, MD, USA.
Mahendra DamarlaDepartment of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Rachel DamicoDepartment of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
James P MaloneyDivision of Pulmonary Sciences and Critical Care Medicine, University of Colorado School of Medicine, Aurora, CO, USA.
Marc MossDivision of Pulmonary Sciences and Critical Care Medicine, University of Colorado School of Medicine, Aurora, CO, USA.
Greg S MartinDepartment of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
Jonathan SevranskyDepartment of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
Carl ShanholtzUniversity of Maryland School of Medicine, Baltimore, MD, USA.
Dan L HerrUniversity of Maryland School of Medicine, Baltimore, MD, USA.
Joe G N GarciaUniversity of Arizona College of Medicine, Tucson, AZ, USA.
Tamara Hernandez-BeeftinkResearch Unit, Hospital Universitario Ntra. Sra. de Candelaria, Santa Cruz de Tenerife, Spain.
Jesús VillarResearch Unit, Hospital Universitario Dr. Negrin, Las Palmas de Gran Canaria, Spain.
Carlos FloresResearch Unit, Hospital Universitario Ntra. Sra. de Candelaria, Santa Cruz de Tenerife, Spain.
Terri H BeatyDepartment of Epidemiology, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, MD, USA.
Roy BrowerDepartment of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Paul M HassounDepartment of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. phassou1@jhmi.edu.
Kathleen C BarnesDivision of Biomedical Informatics & Personalized Medicine, University of Colorado School of Medicine, Aurora, CO, USA. Kathleen.Barnes@cuanschutz.edu.
Johns Hopkins University · USUniversity of Colorado Denver · USEmory University · USHospital Universitario de Gran Canaria Doctor Negrín · ESJohns Hopkins Medicine · USUniversity of Maryland, Baltimore · USCentro de Investigación Biomédica en Red de Enfermedades Respiratorias · ESUniversity of Arizona · US

Funding

VENTILATOR ASSOCIATED LUNG INJURY: MOLECULAR APPROACHESP50HL073994 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI NATARAJAN, VISWANATHAN · 2003 to 2007
$21.3M
Targeting Divergent Roles of Caspase 3 to Promote Endothelial Barrier IntegrityR01HL133413 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI DAMARLA, MAHENDRA · 2016 to 2020
$2.0M
MAP Kinase Signaling in Apoptosis-Induced Ventilator-Associated Lung InjuryK08HL097024 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI DAMARLA, MAHENDRA · 2009 to 2013
$805k
NHLBI NIH HHS K08 HL097024NHLBI NIH HHS L30 HL105116NHLBI NIH HHS P50 HL073994NHLBI NIH HHS R01 HL133413
6 · The paper itself

Abstract

backgroundSepsis and associated organ failures confer substantial morbidity and mortality. Xanthine oxidoreductase (XOR) is implicated in the development of tissue oxidative damage in a wide variety of respiratory and cardiovascular disorders including sepsis and sepsis-associated acute respiratory distress syndrome (ARDS). We examined whether single nucleotide polymorphisms (SNPs) in the XDH gene (encoding XOR) might influence susceptibility to and outcome in patients with sepsis.

methodsWe genotyped 28 tag SNPs in XDH gene in the CELEG cohort, including 621 European American (EA) and 353 African American (AA) sepsis patients. Serum XOR activity was measured in a subset of CELEG subjects. Additionally, we assessed the functional effects of XDH variants utilizing empirical data from different integrated software tools and datasets.

resultsAmong AA patients, six intronic variants (rs206805, rs513311, rs185925, rs561525, rs2163059, rs13387204), in a region enriched with regulatory elements, were associated with risk of sepsis (P < 0.008-0.049). Two out of six SNPs (rs561525 and rs2163059) were associated with risk of sepsis-associated ARDS in an independent validation cohort (GEN-SEP) of 590 sepsis patients of European descent. Two common SNPs (rs1884725 and rs4952085) in tight linkage disequilibrium (LD) provided strong evidence for association with increased levels of serum creatinine (P

conclusionsOur findings suggest that XOR is a novel combined genetic and biochemical marker for risk and outcome in patients with sepsis and ARDS.

Indexed as

Respiratory Distress SyndromeSepsisGenotypeHumansPolymorphism, Single NucleotideXanthine DehydrogenaseXanthine DehydrogenaseAcute respiratory distress syndromeBiomarkerHaplotypeSepsisSingle nucleotide polymorphismXanthine oxidoreductase

Identifiers

PMID37415141
PMCPMC10324226
OpenAlexW4383369115

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.