Genome-wide association study of inhaled corticosteroid response in admixed children with asthma.

Administration, Inhalation Adolescent Adrenal Cortex Hormones / administration & dosage Asthma / genetics Child Cytidine Deaminase / genetics DNA-Binding Proteins / genetics Female GTPase-Activating Proteins / genetics Genome-Wide Association Study Humans Male Minor Histocompatibility Antigens / genetics
African American Latino childhood asthma exacerbations pharmacogenomics

Journal

Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology
ISSN: 1365-2222
Titre abrégé: Clin Exp Allergy
Pays: England
ID NLM: 8906443

Informations de publication

Date de publication:
06 2019
Historique:
received: 06 08 2018
revised: 30 11 2018
accepted: 29 12 2018
pubmed: 31 1 2019
medline: 31 7 2020
entrez: 31 1 2019
Statut: ppublish

Résumé

Inhaled corticosteroids (ICS) are the most widely prescribed and effective medication to control asthma symptoms and exacerbations. However, many children still have asthma exacerbations despite treatment, particularly in admixed populations, such as Puerto Ricans and African Americans. A few genome-wide association studies (GWAS) have been performed in European and Asian populations, and they have demonstrated the importance of the genetic component in ICS response. We aimed to identify genetic variants associated with asthma exacerbations in admixed children treated with ICS and to validate previous GWAS findings. A meta-analysis of two GWAS of asthma exacerbations was performed in 1347 admixed children treated with ICS (Hispanics/Latinos and African Americans), analysing 8.7 million genetic variants. Those with P ≤ 5 × 10 A total of 15 independent variants were suggestively associated with asthma exacerbations in admixed populations (P ≤ 5 × 10 This study revealed the novel association of APOBEC3B and APOBEC3C with asthma exacerbations in children treated with ICS and replicated previously identified genomic regions. This contributes to the current knowledge about the multiple genetic markers determining responsiveness to ICS which could lead in the future the clinical identification of those asthma patients who are not able to respond to such treatment.

Sections du résumé

BACKGROUND
Inhaled corticosteroids (ICS) are the most widely prescribed and effective medication to control asthma symptoms and exacerbations. However, many children still have asthma exacerbations despite treatment, particularly in admixed populations, such as Puerto Ricans and African Americans. A few genome-wide association studies (GWAS) have been performed in European and Asian populations, and they have demonstrated the importance of the genetic component in ICS response.
OBJECTIVE
We aimed to identify genetic variants associated with asthma exacerbations in admixed children treated with ICS and to validate previous GWAS findings.
METHODS
A meta-analysis of two GWAS of asthma exacerbations was performed in 1347 admixed children treated with ICS (Hispanics/Latinos and African Americans), analysing 8.7 million genetic variants. Those with P ≤ 5 × 10
RESULTS
A total of 15 independent variants were suggestively associated with asthma exacerbations in admixed populations (P ≤ 5 × 10
CONCLUSIONS AND CLINICAL RELEVANCE
This study revealed the novel association of APOBEC3B and APOBEC3C with asthma exacerbations in children treated with ICS and replicated previously identified genomic regions. This contributes to the current knowledge about the multiple genetic markers determining responsiveness to ICS which could lead in the future the clinical identification of those asthma patients who are not able to respond to such treatment.

Identifiants

DOI: 10.1111/cea.13354 PMID: 30697902 PMC: PMC7054824
pubmed: 30697902
doi: 10.1111/cea.13354
pmc: PMC7054824
mid: NIHMS1564752
doi:

Substances chimiques

ARHGAP28 protein, human 0
Adrenal Cortex Hormones 0
DNA-Binding Proteins 0
GTPase-Activating Proteins 0
L3MBTL4 protein, human 0
Minor Histocompatibility Antigens 0
APOBEC3B protein, human EC 3.5.4.5
APOBEC3C protein, human EC 3.5.4.5
Cytidine Deaminase EC 3.5.4.5

Types de publication

Clinical Trial Journal Article Multicenter Study Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

789-798

Subventions

Organisme : NIEHS NIH HHS
ID : R01 ES015794
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL141992
Pays : United States
Organisme : Medical Research Council
ID : MR/L006758/1
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : R01 HL128439
Pays : United States
Organisme : NIEHS NIH HHS
ID : R21 ES024844
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL135156
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007546
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL117004
Pays : United States
Organisme : NIMHD NIH HHS
ID : P60 MD006902
Pays : United States
Organisme : NIGMS NIH HHS
ID : RL5 GM118984
Pays : United States
Organisme : NIMHD NIH HHS
ID : R01 MD010443
Pays : United States

Informations de copyright

© 2019 John Wiley & Sons Ltd.

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Auteurs

Natalia Hernandez-Pacheco (N)

Research Unit, Hospital Universitario N.S. de Candelaria, Universidad de La Laguna, San Cristóbal de La Laguna, Spain.
Genomics and Health Group, Department of Biochemistry, Microbiology, Cell Biology and Genetics, Universidad de La Laguna, San Cristóbal de La Laguna, Santa Cruz de Tenerife, Spain.

Niloufar Farzan (N)

Department of Respiratory Medicine, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, Netherlands.
Division of Pharmacoepidemiology and Clinical Pharmacology, Faculty of Science, Utrecht University, Utrecht, Netherlands.

Ben Francis (B)

Department of Women's and Children's Health, University of Liverpool, Liverpool, UK.

Leila Karimi (L)

Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, Netherlands.

Katja Repnik (K)

Center for Human Molecular Genetics and Pharmacogenomics, Faculty of Medicine, University of Maribor, Maribor, Slovenia.
Laboratory for Biochemistry, Molecular Biology and Genomics, Faculty for Chemistry and Chemical Engineering, University of Maribor, Maribor, Slovenia.

Susanne J Vijverberg (SJ)

Department of Respiratory Medicine, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, Netherlands.
Division of Pharmacoepidemiology and Clinical Pharmacology, Faculty of Science, Utrecht University, Utrecht, Netherlands.

Patricia Soares (P)

Academic Department of Paediatrics, Brighton and Sussex Medical School, Royal Alexandra Children's Hospital, Brighton, UK.

Maximilian Schieck (M)

Department of Pediatric Pneumology and Allergy, University Children's Hospital Regensburg (KUNO), Regensburg, Germany.
Department of Human Genetics, Hannover Medical School, Hannover, Germany.

Mario Gorenjak (M)

Center for Human Molecular Genetics and Pharmacogenomics, Faculty of Medicine, University of Maribor, Maribor, Slovenia.

Erick Forno (E)

Division of Pediatric Pulmonary Medicine, Children's Hospital of Pittsburgh of the University of Pittsburgh, Medical Center, University of Pittsburgh, Pittsburgh, Pennsylvania.

Celeste Eng (C)

Department of Medicine, University of California, San Francisco, California.

Sam S Oh (SS)

Department of Medicine, University of California, San Francisco, California.

Lina Pérez-Méndez (L)

Department of Clinic Epidemiology and Biostatistics, Research Unit, Hospital Universitario N.S. de Candelaria, Gerencia de Atención Primaria, Santa Cruz de Tenerife, Spain.
CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain.

Vojko Berce (V)

Center for Human Molecular Genetics and Pharmacogenomics, Faculty of Medicine, University of Maribor, Maribor, Slovenia.
Department of Pediatrics, University Medical Centre Maribor, Maribor, Slovenia.

Roger Tavendale (R)

Population Pharmacogenetics Group, Biomedical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK.

Lesly-Anne Samedy (LA)

Department of Medicine, University of California, San Francisco, California.
Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, California.

Scott Hunstman (S)

Department of Medicine, University of California, San Francisco, California.

Donglei Hu (D)

Department of Medicine, University of California, San Francisco, California.

Kelley Meade (K)

Children's Hospital and Research Center Oakland, Oakland, California.

Harold J Farber (HJ)

Department of Pediatrics, Section of Pulmonology, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas.

Pedro C Avila (PC)

Department of Medicine, Northwestern University, Chicago, Illinois.
Allergy & ENT Associates, The Woodland, Texas.

Denise Serebrisky (D)

Pediatric Pulmonary Division, New York, NY.

Shannon M Thyne (SM)

Department of Pediatrics, University of California, San Francisco, California.

Emerita Brigino-Buenaventura (E)

Department of Allergy and Immunology, Vallejo, California.

William Rodriguez-Cintron (W)

Veterans Caribbean Health Care System, San Juan, Puerto Rico.

Saunak Sen (S)

University of Tennessee Health Science Center, Memphis, Tennessee.

Rajesh Kumar (R)

Feinberg School of Medicine's Division of Allergy and Immunology, Northwestern University, Chicago, Illinois.
Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois.

Michael Lenoir (M)

Bay Area Pediatrics, Oakland, California.

Jose R Rodriguez-Santana (JR)

Centro de Neumología Pediátrica, San Juan, Puerto Rico.

Juan C Celedón (JC)

Division of Pediatric Pulmonary Medicine, Children's Hospital of Pittsburgh of the University of Pittsburgh, Medical Center, University of Pittsburgh, Pittsburgh, Pennsylvania.

Somnath Mukhopadhyay (S)

Academic Department of Paediatrics, Brighton and Sussex Medical School, Royal Alexandra Children's Hospital, Brighton, UK.
Population Pharmacogenetics Group, Biomedical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK.

Uroš Potočnik (U)

Center for Human Molecular Genetics and Pharmacogenomics, Faculty of Medicine, University of Maribor, Maribor, Slovenia.
Laboratory for Biochemistry, Molecular Biology and Genomics, Faculty for Chemistry and Chemical Engineering, University of Maribor, Maribor, Slovenia.

Munir Pirmohamed (M)

Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.

Katia M Verhamme (KM)

Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, Netherlands.

Michael Kabesch (M)

Department of Pediatric Pneumology and Allergy, University Children's Hospital Regensburg (KUNO), Regensburg, Germany.

Colin N A Palmer (CNA)

Population Pharmacogenetics Group, Biomedical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK.

Daniel B Hawcutt (DB)

Department of Women's and Children's Health, University of Liverpool, Liverpool, UK.
Alder Hey Children's Hospital, Liverpool, UK.

Carlos Flores (C)

Research Unit, Hospital Universitario N.S. de Candelaria, Universidad de La Laguna, San Cristóbal de La Laguna, Spain.
CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain.
Genomics Division, Instituto Tecnológico y de Energías Renovables (ITER), Santa Cruz de Tenerife, Spain.

Anke H Maitland-van der Zee (AH)

Department of Respiratory Medicine, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, Netherlands.
Division of Pharmacoepidemiology and Clinical Pharmacology, Faculty of Science, Utrecht University, Utrecht, Netherlands.
Department of Pediatric Respiratory Medicine and Allergy, Emma's Children Hospital, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, Netherlands.

Esteban G Burchard (EG)

Department of Medicine, University of California, San Francisco, California.
Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, California.

Maria Pino-Yanes (M)

Research Unit, Hospital Universitario N.S. de Candelaria, Universidad de La Laguna, San Cristóbal de La Laguna, Spain.
Genomics and Health Group, Department of Biochemistry, Microbiology, Cell Biology and Genetics, Universidad de La Laguna, San Cristóbal de La Laguna, Santa Cruz de Tenerife, Spain.
CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain.

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Classifications MeSH

questionsmedicales.fr › Thérapeutique › Traitement médicamenteux › Voies d'administration de substances chimiques et des médicaments › Administration par inhalation › Genome-wide association study of inhaled...
questionsmedicales.fr › Personnes › Tranches d'âge › Adolescent › Genome-wide association study of inhaled...
questionsmedicales.fr › Hormones corticosurrénaliennes › Genome-wide association study of inhaled...
questionsmedicales.fr › Maladies du système immunitaire › Hypersensibilité › Hypersensibilité immédiate › Hypersensibilité respiratoire › Asthme › Genome-wide association study of inhaled...
questionsmedicales.fr › Personnes › Tranches d'âge › Enfant › Genome-wide association study of inhaled...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Hydrolases › Aminohydrolases › Nucleoside deaminases › Cytidine deaminase › Genome-wide association study of inhaled...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de liaison à l'ADN › Genome-wide association study of inhaled...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Régulateurs des protéines G › Protéines d'activation de la GTPase › Genome-wide association study of inhaled...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Épidémiologie moléculaire › Étude d'association pangénomique › Genome-wide association study of inhaled...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Genome-wide association study of inhaled...
questionsmedicales.fr › Facteurs biologiques › Antigènes › Isoantigènes › Antigènes d'histocompatibilité › Antigènes mineurs d'histocompatibilité › Genome-wide association study of inhaled...