Epigenomic response to albuterol treatment in asthma-relevant airway epithelial cells.


Journal

Clinical epigenetics
ISSN: 1868-7083
Titre abrégé: Clin Epigenetics
Pays: Germany
ID NLM: 101516977

Informations de publication

Date de publication:
03 10 2023
Historique:
received: 02 03 2023
accepted: 25 09 2023
medline: 4 10 2023
pubmed: 3 10 2023
entrez: 2 10 2023
Statut: epublish

Résumé

Albuterol is the first-line asthma medication used in diverse populations. Although DNA methylation (DNAm) is an epigenetic mechanism involved in asthma and bronchodilator drug response (BDR), no study has assessed whether albuterol could induce changes in the airway epithelial methylome. We aimed to characterize albuterol-induced DNAm changes in airway epithelial cells, and assess potential functional consequences and the influence of genetic variation and asthma-related clinical variables. We followed a discovery and validation study design to characterize albuterol-induced DNAm changes in paired airway epithelial cultures stimulated in vitro with albuterol. In the discovery phase, an epigenome-wide association study using paired nasal epithelial cultures from Puerto Rican children (n = 97) identified 22 CpGs genome-wide associated with repeated-use albuterol treatment (p < 9 × 10 This study revealed evidence of epigenetic modifications induced by albuterol in the mucociliary airway epithelium. The epigenomic response induced by albuterol might have potential clinical implications by affecting biological pathways relevant to asthma.

Sections du résumé

BACKGROUND
Albuterol is the first-line asthma medication used in diverse populations. Although DNA methylation (DNAm) is an epigenetic mechanism involved in asthma and bronchodilator drug response (BDR), no study has assessed whether albuterol could induce changes in the airway epithelial methylome. We aimed to characterize albuterol-induced DNAm changes in airway epithelial cells, and assess potential functional consequences and the influence of genetic variation and asthma-related clinical variables.
RESULTS
We followed a discovery and validation study design to characterize albuterol-induced DNAm changes in paired airway epithelial cultures stimulated in vitro with albuterol. In the discovery phase, an epigenome-wide association study using paired nasal epithelial cultures from Puerto Rican children (n = 97) identified 22 CpGs genome-wide associated with repeated-use albuterol treatment (p < 9 × 10
CONCLUSIONS
This study revealed evidence of epigenetic modifications induced by albuterol in the mucociliary airway epithelium. The epigenomic response induced by albuterol might have potential clinical implications by affecting biological pathways relevant to asthma.

Identifiants

pubmed: 37784136
doi: 10.1186/s13148-023-01571-0
pii: 10.1186/s13148-023-01571-0
pmc: PMC10546710
doi:

Substances chimiques

Albuterol QF8SVZ843E
Bronchodilator Agents 0

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

156

Subventions

Organisme : NIEHS NIH HHS
ID : R01 ES015794
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL120393
Pays : United States
Organisme : NIEHS NIH HHS
ID : R01ES015794, R21ES24844
Pays : United States
Organisme : NHGRI NIH HHS
ID : UM1 HG008901
Pays : United States
Organisme : NIMHD NIH HHS
ID : R01MD010443, R56MD013312
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL135156
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL128439
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL117004
Pays : United States
Organisme : NIEHS NIH HHS
ID : R21 ES024844
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL117626
Pays : United States
Organisme : NHGRI NIH HHS
ID : U24 HG008956
Pays : United States
Organisme : NIMHD NIH HHS
ID : R56 MD013312
Pays : United States
Organisme : NIMHD NIH HHS
ID : R01 MD010443
Pays : United States
Organisme : NIEHS NIH HHS
ID : HHSN268201600032C
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL155024
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01HL155024-01, HHSN268201600032I, 3R01HL-117626-02S1, HHSN268201800002I, 3R01HL117004-02S3, 3R01HL-120393-02S1, R01HL117004, R01HL128439, R01HL135156, X01HL134589
Pays : United States

Informations de copyright

© 2023. BioMed Central Ltd., part of Springer Nature.

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Auteurs

Javier Perez-Garcia (J)

Genomics and Health Group, Department of Biochemistry, Microbiology, Cell Biology, and Genetics, Universidad de La Laguna (ULL), La Laguna, Tenerife, Canary Islands, Spain. jpegarci@ull.edu.es.

Maria Pino-Yanes (M)

Genomics and Health Group, Department of Biochemistry, Microbiology, Cell Biology, and Genetics, Universidad de La Laguna (ULL), La Laguna, Tenerife, Canary Islands, Spain. mdelpino@ull.edu.es.
CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain. mdelpino@ull.edu.es.
Instituto de Tecnologías Biomédicas (ITB), Universidad de La Laguna (ULL), La Laguna, Spain. mdelpino@ull.edu.es.

Elizabeth G Plender (EG)

Center for Genes, Environment, and Health, National Jewish Health, Denver, CO, USA.

Jamie L Everman (JL)

Center for Genes, Environment, and Health, National Jewish Health, Denver, CO, USA.

Celeste Eng (C)

Department of Medicine, University of California San Francisco (UCSF), San Francisco, CA, USA.

Nathan D Jackson (ND)

Center for Genes, Environment, and Health, National Jewish Health, Denver, CO, USA.

Camille M Moore (CM)

Center for Genes, Environment, and Health, National Jewish Health, Denver, CO, USA.
Department of Biomedical Research, National Jewish Health, Denver, CO, USA.
Department of Biostatistics and Informatics, University of Colorado, Denver, CO, USA.

Kenneth B Beckman (KB)

University of Minnesota Genomics Center (UMNGC), Minneapolis, MN, USA.

Vivian Medina (V)

Centro de Neumología Pediátrica, San Juan, PR, USA.

Sunita Sharma (S)

Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado School of Medicine, Aurora, CO, USA.

Daniel Efrain Winnica (DE)

Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado School of Medicine, Aurora, CO, USA.

Fernando Holguin (F)

Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado School of Medicine, Aurora, CO, USA.

José Rodríguez-Santana (J)

Centro de Neumología Pediátrica, San Juan, PR, USA.

Jesús Villar (J)

CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain.
Multidisciplinary Organ Dysfunction Evaluation Research Network (MODERN), Research Unit, Hospital Universitario Dr. Negrín, Las Palmas de Gran Canaria, Spain.
Li Ka Shing Knowledge Institute at the St. Michael's Hospital, Toronto, ON, Canada.

Elad Ziv (E)

Institute for Human Genetics, University of California San Francisco (UCSF), San Francisco, CA, USA.
Department of Epidemiology and Biostatistics, University of California, San Francisco School of Medicine, San Francisco, CA, USA.

Max A Seibold (MA)

Center for Genes, Environment, and Health, National Jewish Health, Denver, CO, USA.
Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado School of Medicine, Aurora, CO, USA.
Department of Pediatrics, National Jewish Health, Denver, CO, USA.

Esteban G Burchard (EG)

Department of Medicine, University of California San Francisco (UCSF), San Francisco, CA, USA.
Department of Bioengineering and Therapeutic Sciences, University of California San Francisco (UCSF), San Francisco, CA, USA.

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