Evidence map›Paper›PMID 25616159›Full record

SynthesisClinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology2015

ST13 polymorphisms and their effect on exacerbations in steroid-treated asthmatic children and young adults.

S J H Vijverberg, E S Koster, R Tavendale, M Leusink, L Koenderman, J A M Raaijmakers, D S Postma, G H Koppelman, S W Turner, S Mukhopadhyay and 10 more

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

Synthesis in Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 3 pooled it
2.5field-weighted citation impact, top 11% 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

18 citing papers in PubMed, 3 syntheses or guidelines pooled it, 22 citations in OpenAlex.

  1. Pooled it
  2. Genome-wide association studies of exacerbations in children using long-acting beta2-agonists.Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology · 2021
    Pooled it
  3. Pooled it
  4. Pharmacogenetics of childhood uncontrolled asthma.Expert review of clinical immunology · 2025
    Review
  5. Article
  6. Genes · 2024
    Article
  7. Article
  8. [Liver failure and glucocorticoid resistance].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2020
    Article
  9. Advances in asthma and allergic disease genetics: Is bigger always better?The Journal of allergy and clinical immunology · 2019
    Review
  10. Article
  11. How does race and ethnicity effect the precision treatment of asthma?Expert review of precision medicine and drug development · 2019
    Article
  12. Review
  13. Article
  14. Genetic Signatures of Asthma Exacerbation.Allergy, asthma & immunology research · 2017
    Review
  15. Article
  16. Personalized management of asthma exacerbations: lessons from genetic studies.Expert review of precision medicine and drug development · 2016
    Article
  17. Article
  18. Pharmacogenetics of Asthma.Indian journal of pediatrics · 2015
    Article
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

20 authors at 12 institutions in 5 countries.

S J H VijverbergDivision of Pharmacoepidemiology & Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Faculty of Science, Utrecht University, Utrecht, The Netherlands.
E S KosterDivision of Pharmacoepidemiology & Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Faculty of Science, Utrecht University, Utrecht, The Netherlands.
R TavendalePopulation Pharmacogenetics Group, Biomedical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK.
M LeusinkDivision of Pharmacoepidemiology & Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Faculty of Science, Utrecht University, Utrecht, The Netherlands.
L KoendermanDepartment of Respiratory Medicine, University Medical Centre Utrecht, Utrecht, The Netherlands.
J A M RaaijmakersDivision of Pharmacoepidemiology & Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Faculty of Science, Utrecht University, Utrecht, The Netherlands.
D S PostmaDepartment of Pulmonology, Groningen Research Institute for Asthma and COPD, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
G H KoppelmanDepartment of Paediatric Pulmonology and Paediatric Allergology, Beatrix Children's Hospital, Groningen Research Institute for Asthma and COPD, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
S W TurnerDepartment of Child Health, University of Aberdeen, Aberdeen, UK.
S MukhopadhyayPopulation Pharmacogenetics Group, Biomedical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK.
S M TseChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
K G TantisiraChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
D B HawcuttDepartment of Women's and Children's Health, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
B FrancisDepartment of Biostatistics, University of Liverpool, Liverpool, UK.
M PirmohamedDepartment of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
M Pino-YanesDepartment of Medicine, University of California, San Francisco, CA, USA.
C EngDepartment of Medicine, University of California, San Francisco, CA, USA.
E G BurchardDepartment of Medicine, University of California, San Francisco, CA, USA.
C N A PalmerPopulation Pharmacogenetics Group, Biomedical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK.
A H Maitland-van der ZeeDivision of Pharmacoepidemiology & Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Faculty of Science, Utrecht University, Utrecht, The Netherlands.
Utrecht University · NLUniversity of Liverpool · GBBrigham and Women's Hospital · USUniversity Medical Center Utrecht · NLUniversity of California, San Francisco · USInstituto de Salud Carlos III · ESNinewells Hospital · GBRoyal Alexandra Children's Hospital · GBUniversity Medical Center Groningen · NLUniversity of Aberdeen · GBUniversity of Dundee · GBUniversity of Groningen · NL

Funding

THE PHARMACOGENETICS OF ASTHMA TREATMENTU01HL065899 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI TANTISIRA, KELAN G, WEISS, SCOTT T · 2000 to 2014
$38.5M
New Approaches for Empowering Studies of Asthma in Populations of African DescentR01HL104608 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI BARNES, KATHLEEN C, KENNY, EIMEAR ELIZABETH · 2011 to 2022
$23.1M
The Airway Functional Genomics of Bronchodilator Drug Response in Minority Children with AsthmaR01HL117004 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI AHITUV, NADAV, SEIBOLD, MAX A · 2013 to 2022
$9.3M
CLINICAL, PHARMACOLOGY, DRUG ACTION &PHARMACOKINETICST32GM007546 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Radojka Savic · 1985 to 2026
$8.9M
Social Interventions to address disparities In young adult tobacco useP60MD006902 · NIMHD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BURCHARD, ESTEBAN GONZALEZ · 2012 to 2016
$6.4M
Gene-environments and Admixture in Latino Asthmatics (GALA 2)R01ES015794 · NIEHS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BURCHARD, ESTEBAN GONZALEZ · 2008 to 2012
$5.4M
Whole Genome Analyses for Asthma in Latino PopulationsR01HL088133 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BURCHARD, ESTEBAN GONZALEZ · 2008 to 2012
$3.8M
INTEGRATIVE PHARMACOGENOMICS OF LEUKOTRIENE INHIBITION IN ASTHMAR01HL092197 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI TANTISIRA, KELAN G · 2009 to 2013
$3.6M
Case-control Association Studies and Genetic ConfoundingR01HL078885 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BURCHARD, ESTEBAN GONZALEZ · 2005 to 2009
$1.9M
GENOMICS AND PHARMACOGENOMICS OF SYMPTOMS IN ASTHMAR01NR013391 · NINR · BRIGHAM AND WOMEN'S HOSPITAL · PI TANTISIRA, KELAN G · 2011 to 2013
$1.3M
Genetics of Asthma In Latino AmericansK23HL004464 · NHLBI · UNIVERSITY OF CALIFORNIA SAN FRANCISCO · PI BURCHARD, ESTEBAN GONZALEZ · 2001 to 2005
$609k
Pharmacogenetic Linkage of Corticosteroid Response: Asthma Therapy ImplicationsK23HG003983 · NHGRI · BRIGHAM AND WOMEN'S HOSPITAL · PI TANTISIRA, KELAN G · 2006 to 2008
$485k
Chief Scientist Office CZH/4/418Medical Research Council MR/L006758/1NHGRI NIH HHS K23 HG003983NHLBI NIH HHS HL004464NHLBI NIH HHS HL078885NHLBI NIH HHS HL088133NHLBI NIH HHS HL104608NHLBI NIH HHS HL117004NHLBI NIH HHS K23 HL004464NHLBI NIH HHS R01 HL078885NHLBI NIH HHS R01 HL088133NHLBI NIH HHS R01 HL092197NHLBI NIH HHS R01 HL092917NHLBI NIH HHS R01 HL104608NHLBI NIH HHS R01 HL117004NHLBI NIH HHS U01 HL065899NIEHS NIH HHS ES015794NIEHS NIH HHS R01 ES015794NIGMS NIH HHS GM007546NIGMS NIH HHS T32 GM007546NIMHD NIH HHS MD006902NIMHD NIH HHS P60 MD006902NINR NIH HHS R01 NR013391
6 · The paper itself

Abstract

backgroundThe clinical response to inhaled corticosteroids (ICS) is associated with single nucleotide polymorphisms (SNPs) in various genes. This study aimed to relate variations in genes in the steroid pathway and asthma susceptibility genes to exacerbations in children and young adults treated with ICS.

methodsWe performed a meta-analysis of three cohort studies: Pharmacogenetics of Asthma Medication in Children: Medication with Anti-Inflammatory effects (n = 357, age: 4-12 years, the Netherlands), BREATHE (n = 820, age: 3-22 years, UK) and Paediatric Asthma Gene Environment Study (n = 391, age: 2-16 years, UK). Seventeen genes were selected based on a role in the glucocorticoid signalling pathway or a reported association with asthma. Two outcome parameters were used to reflect exacerbations: hospital visits and oral corticosteroid (OCS) use in the previous year. The most significant associations were tested in three independent validation cohorts; the Childhood Asthma Management Programme (clinical trial, n = 172, age: 5-12 years, USA), the Genes- environment and Mixture in Latino Americans II- study (n = 745, age: 8-21, USA) and the Pharmacogenetics of adrenal suppression cohort (n = 391, age: 5-18, UK) to test the robustness of the findings. Finally, all results were meta-analysed.

resultsTwo SNPs in ST13 (rs138335 and rs138337), but not in the other genes, were associated at a nominal level with an increased risk of exacerbations in asthmatics using ICS in the three cohorts studied. In a meta-analysis of all six studies, ST13 rs138335 remained associated with an increased risk of asthma-related hospital visits and OCS use in the previous year; OR = 1.22 (P = 0.013) and OR = 1.22 (P = 0.0017), respectively. CONCLUSION AND CLINICAL RELEVANCE: A novel susceptibility gene, ST13, coding for a cochaperone of the glucocorticoid receptor, is associated with exacerbations in asthmatic children and young adults despite their ICS use. Genetic variation in the glucocorticoid signalling pathway may contribute to the interindividual variability in clinical response to ICS treatment in children and young adults.

Indexed as

Polymorphism, Single NucleotideAdolescentAdrenal Cortex HormonesAnti-Asthmatic AgentsAsthmaCarrier ProteinsChildChild, PreschoolCohort StudiesDisease ProgressionFemaleHumansMaleMolecular ChaperonesOdds RatioTreatment OutcomeAdrenal Cortex HormonesAnti-Asthmatic AgentsCarrier ProteinsMolecular ChaperonesST13 protein, humanTumor Suppressor Proteinschildhood asthmacorticosteroidsexacerbationspharmacogenomicsST13

Identifiers

PMID25616159
PMCPMC4461653
OpenAlexW2160364718

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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.