Evidence map›Paper›PMID 25055195›Full record

Observational studyPediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies2014

A single nucleotide polymorphism in the corticotropin receptor gene is associated with a blunted cortisol response during pediatric critical illness.

David Jardine, Mary Emond, Kathleen L Meert, Rick Harrison, Joseph A Carcillo, Kanwaljeet J S Anand, John Berger, Christopher J L Newth, Douglas F Willson, Carol Nicholson and 3 more

Open access · greenAbstract readObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.9field-weighted citation impact, top 24% 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

4 citing papers in PubMed, 9 citations in OpenAlex.

  1. Review
  2. Article
  3. Glucocorticoid Receptor Polymorphisms and Outcomes in Pediatric Septic Shock.Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies · 2017
    Article
  4. Identifying critically ill patients who may benefit from adjunctive corticosteroids: not as easy as we thought.Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies · 2014
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 9 institutions in 1 country.

David Jardine1Department of Anesthesiology, University of Washington School of Medicine, Seattle, WA. 2Department of Biostatistics, University of Washington School of Medicine, Seattle, WA. 3Department of Pediatrics, Children's Hospital of Michigan, Detroit, MI. 4Department of Pediatrics, University of California at Los Angeles, Los Angeles, CA. 5Department of Critical Care Medicine, Children's Hospital of Pittsburgh, Pittsburgh, PA. 6Department of Pediatrics, Le Bonheur Children's Hospital and University of Tennessee Health Science Center, Memphis, TN. 7Department of Pediatrics, Children's National Medical Center, Washington, DC. 8Department of Anesthesiology and Critical Care Medicine, Children's Hospital Los Angeles, Los Angeles, CA. 9Department of Pediatrics, University of Virginia Children's Hospital, Charlottesville, VA. 10Eunice Kennedy Shriver, National Institute of Child Health and Human Development, Washington, D.C. 11Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, UT. 12Department of Pediatrics, University of Washington School of Medicine, Seattle, WA.
Mary Emond
Kathleen L Meert
Rick Harrison
Joseph A Carcillo
Kanwaljeet J S Anand
John Berger
Christopher J L Newth
Douglas F Willson
Carol Nicholson
J Michael Dean
Jerry J Zimmerman
Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network
University of Washington · USChildren's Hospital of Los Angeles · USChildren's Hospital of Michigan · USChildren's Hospital of Pittsburgh · USChildren's National · USUniversity of California, Los Angeles · USUniversity of Tennessee Health Science Center · USUniversity of Utah · USUniversity of Virginia · US

Funding

Data Coordinating Center for the Collaborative Pediatric Critical Care Research NetworkU01HD049934 · NICHD · UNIVERSITY OF UTAH · PI DEAN, JONATHAN MICHAEL · 2005 to 2020
$35.2M
Physiologically Guided Ventilator Strategies in ChildrenU10HD050012 · NICHD · CHILDREN'S HOSPITAL OF LOS ANGELES · PI NEWTH, CHRISTOPHER JOHN · 2005 to 2014
$3.7M
Neurodevelopmental Outcome after Cardiac Intensive CareU10HD049981 · NICHD · CHILDREN'S RESEARCH INSTITUTE · PI WESSEL, DAVID LLOYD · 2005 to 2014
$3.7M
Collaborative Pediatric Critical Care Research NetworkU10HD050096 · NICHD · WAYNE STATE UNIVERSITY · PI MEERT, KATHLEEN L. · 2005 to 2014
$3.2M
Metoclopramide prevents PICU nosocomial infectionU10HD049983 · NICHD · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CARCILLO, JOSEPH A · 2005 to 2014
$3.1M
Life After Pediatric Sepsis Evaluation, LAPSER01HD073362 · NICHD · SEATTLE CHILDREN'S HOSPITAL · PI ZIMMERMAN, JERRY JOHN · 2013 to 2017
$3.1M
Collaborative Pediatric Critical Care Research NetworkUG1HD050096 · NICHD · WAYNE STATE UNIVERSITY · PI MEERT, KATHLEEN L. · 2015 to 2020
$1.6M
1st Tier Drugs+Theophylline in Pediatric Severe AsthmaU10HD049945 · NICHD · SEATTLE CHILDREN'S HOSPITAL · PI ZIMMERMAN, JERRY JOHN · 2005 to 2010
$1.6M
Collaborative Pediatric Critical Care Research Network - Clinical SiteRL1HD107773 · NICHD · CENTRAL MICHIGAN UNIVERSITY · PI KATHLEEN L. MEERT · 2021 to 2026
$862k
NICHD NIH HHS 3U10HD049945-05S1NICHD NIH HHS R01 HD073362NICHD NIH HHS RL1 HD107773NICHD NIH HHS U01 HD049934NICHD NIH HHS U01HD049934NICHD NIH HHS U10 HD049945NICHD NIH HHS U10HD049945NICHD NIH HHS U10 HD049981NICHD NIH HHS U10HD049981NICHD NIH HHS U10 HD049983NICHD NIH HHS U10HD049983NICHD NIH HHS U10 HD050012NICHD NIH HHS U10HD050012NICHD NIH HHS U10 HD050096NICHD NIH HHS U10HD050096NICHD NIH HHS U10HD500009NICHD NIH HHS UG1 HD050096
6 · The paper itself

Abstract

objectivesThe cortisol response during critical illness varies widely among patients. Our objective was to examine single nucleotide polymorphisms in candidate genes regulating cortisol synthesis, metabolism, and activity to determine if genetic differences were associated with variability in the cortisol response among critically ill children.

designThis was a prospective observational study employing tag single nucleotide polymorphism methodology to examine genetic contributions to the variability of the cortisol response in critical illness. Thirty-one candidate genes and 31 ancestry markers were examined.

settingPatients were enrolled from seven pediatric critical care units that constitute the Eunice Kennedy Shriver Collaborative Pediatric Critical Care Research Network. SUBJECTS: Critically ill children (n = 92), age 40 weeks gestation to 18 years old, were enrolled.

interventionsBlood samples were obtained from all patients for serum cortisol measurements and DNA isolation. Demographic and illness severity data were collected. MEASUREMENTS AND MAIN

resultsSingle nucleotide polymorphisms were tested for association with serum free cortisol concentrations in context of higher illness severity as quantified by Pediatric Risk of Mortality III score greater than 7. A single nucleotide polymorphism (rs1941088) in the MC2R gene was strongly associated (p = 0.0005) with a low free cortisol response to critical illness. Patients with the AA genotype were over seven times more likely to have a low free cortisol response to critical illness than those with a GG genotype. Patients with the GA genotype exhibited an intermediate free cortisol response to critical illness.

conclusionsThe A allele at rs1941088 in the MC2R gene, which encodes the adrenocorticotropic hormone (corticotropin, ACTH) receptor, is associated with a low cortisol response in critically ill children. These data provide evidence for a genetic basis for a portion of the variability in cortisol production during critical illness. Independent replication of these findings will be important and could facilitate development of personalized treatment for patients with a low cortisol response to severe illness.

Indexed as

Critical IllnessPolymorphism, Single NucleotideAdolescentAdrenal Cortex HormonesAllelesChildChild, PreschoolDNAFemaleGenotypeHumansHydrocortisoneInfantInfant, NewbornMaleProspective StudiesAdrenal Cortex HormonesDNAHydrocortisoneNR3C2 protein, humanReceptor, Melanocortin, Type 2Receptors, MineralocorticoidTumor Necrosis Factor-alpha

Identifiers

PMID25055195
PMCPMC4712687
OpenAlexW2118226906

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.