Epigenome-Wide Association Studies of the Fractional Exhaled Nitric Oxide and Bronchodilator Drug Response in Moderate-to-Severe Pediatric Asthma.

Autor: Martin-Almeida M; Genomics and Health Group, Department of Biochemistry, Microbiology, Cell Biology, and Genetics, Universidad de La Laguna (ULL), 38200 San Cristóbal de La Laguna, Spain., Perez-Garcia J; Genomics and Health Group, Department of Biochemistry, Microbiology, Cell Biology, and Genetics, Universidad de La Laguna (ULL), 38200 San Cristóbal de La Laguna, Spain., Herrera-Luis E; Genomics and Health Group, Department of Biochemistry, Microbiology, Cell Biology, and Genetics, Universidad de La Laguna (ULL), 38200 San Cristóbal de La Laguna, Spain., Rosa-Baez C; Genomics and Health Group, Department of Biochemistry, Microbiology, Cell Biology, and Genetics, Universidad de La Laguna (ULL), 38200 San Cristóbal de La Laguna, Spain., Gorenjak M; Center for Human Molecular Genetics and Pharmacogenomics, Faculty of Medicine, University of Maribor, 2000 Maribor, Slovenia., Neerincx AH; Department of Respiratory Medicine, Amsterdam University Medical Centres-Loc. AMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands., Sardón-Prado O; Division of Pediatric Respiratory Medicine, Donostia University Hospital, 20014 San Sebastián, Spain.; Department of Pediatrics, University of the Basque Country (UPV/EHU), 48013 San Sebastián, Spain., Toncheva AA; Department of Pediatric Pneumology and Allergy, University Children's Hospital Regensburg (KUNO) at the Hospital St. Hedwig of the Order of St. John, University of Regensburg, D-93049 Regensburg, Germany., Harner S; Department of Pediatric Pneumology and Allergy, University Children's Hospital Regensburg (KUNO) at the Hospital St. Hedwig of the Order of St. John, University of Regensburg, D-93049 Regensburg, Germany., Wolff C; Department of Pediatric Pneumology and Allergy, University Children's Hospital Regensburg (KUNO) at the Hospital St. Hedwig of the Order of St. John, University of Regensburg, D-93049 Regensburg, Germany., Brandstetter S; Department of Pediatric Pneumology and Allergy, University Children's Hospital Regensburg (KUNO) at the Hospital St. Hedwig of the Order of St. John, University of Regensburg, D-93049 Regensburg, Germany., Valletta E; Department of Pediatric Pneumology and Allergy, University Children's Hospital Regensburg (KUNO) at the Hospital St. Hedwig of the Order of St. John, University of Regensburg, D-93049 Regensburg, Germany., Abdel-Aziz MI; Department of Respiratory Medicine, Amsterdam University Medical Centres-Loc. AMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.; Department of Clinical Pharmacy, Faculty of Pharmacy, Assiut University, Assiut 71515, Egypt., Hashimoto S; Department of Respiratory Medicine, Amsterdam University Medical Centres-Loc. AMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.; Department of Pediatric Respiratory Medicine, Emma Children's Hospital, Amsterdam UMC, 1105 AZ Amsterdam, The Netherlands., Berce V; Center for Human Molecular Genetics and Pharmacogenomics, Faculty of Medicine, University of Maribor, 2000 Maribor, Slovenia.; Clinic of Pediatrics, University Medical Centre Maribor, 2000 Maribor, Slovenia., Corcuera-Elosegui P; Division of Pediatric Respiratory Medicine, Donostia University Hospital, 20014 San Sebastián, Spain., Korta-Murua J; Division of Pediatric Respiratory Medicine, Donostia University Hospital, 20014 San Sebastián, Spain.; Department of Pediatrics, University of the Basque Country (UPV/EHU), 48013 San Sebastián, Spain., Buntrock-Döpke H; Department of Pediatric Pneumology and Allergy, University Children's Hospital Regensburg (KUNO) at the Hospital St. Hedwig of the Order of St. John, University of Regensburg, D-93049 Regensburg, Germany., Vijverberg SJH; Department of Respiratory Medicine, Amsterdam University Medical Centres-Loc. AMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands., Verster JC; Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CG Utrecht, The Netherlands.; Centre for Human Psychopharmacology, Swinburne University, Melbourne, VIC 3122, Australia., Kerssemakers N; Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CG Utrecht, The Netherlands., Hedman AM; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, 171 77 Stockholm, Sweden., Almqvist C; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, 171 77 Stockholm, Sweden., Villar J; CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, 28029 Madrid, Spain.; Multidisciplinary Organ Dysfunction Evaluation Research Network, Research Unit, Hospital Universitario Dr. Negrín, 35010 Las Palmas de Gran Canaria, Spain., Kraneveld AD; Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CG Utrecht, The Netherlands., Potočnik U; Center for Human Molecular Genetics and Pharmacogenomics, Faculty of Medicine, University of Maribor, 2000 Maribor, Slovenia.; Clinic of Pediatrics, University Medical Centre Maribor, 2000 Maribor, Slovenia.; Laboratory for Biochemistry, Molecular Biology, and Genomics, Faculty of Chemistry and Chemical Engineering, University of Maribor, 2000 Maribor, Slovenia., Kabesch M; Department of Pediatric Pneumology and Allergy, University Children's Hospital Regensburg (KUNO) at the Hospital St. Hedwig of the Order of St. John, University of Regensburg, D-93049 Regensburg, Germany., Zee AHM; Department of Respiratory Medicine, Amsterdam University Medical Centres-Loc. AMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.; Department of Pediatric Respiratory Medicine, Emma Children's Hospital, Amsterdam UMC, 1105 AZ Amsterdam, The Netherlands., Pino-Yanes M; Genomics and Health Group, Department of Biochemistry, Microbiology, Cell Biology, and Genetics, Universidad de La Laguna (ULL), 38200 San Cristóbal de La Laguna, Spain.; CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, 28029 Madrid, Spain.; Instituto de Tecnologías Biomédicas (ITB), Universidad de La Laguna (ULL), 38200 San Cristóbal de La Laguna, Spain., On Behalf Of The SysPharmPediA Consortium
Jazyk: angličtina
Zdroj: Biomedicines [Biomedicines] 2023 Feb 23; Vol. 11 (3). Date of Electronic Publication: 2023 Feb 23.
DOI: 10.3390/biomedicines11030676
Abstrakt: Asthma is the most prevalent pediatric chronic disease. Bronchodilator drug response (BDR) and fractional exhaled nitric oxide (FeNO) are clinical biomarkers of asthma. Although DNA methylation (DNAm) contributes to asthma pathogenesis, the influence of DNAm on BDR and FeNO is scarcely investigated. This study aims to identify DNAm markers in whole blood associated either with BDR or FeNO in pediatric asthma. We analyzed 121 samples from children with moderate-to-severe asthma. The association of genome-wide DNAm with BDR and FeNO has been assessed using regression models, adjusting for age, sex, ancestry, and tissue heterogeneity. Cross-tissue validation was assessed in 50 nasal samples. Differentially methylated regions (DMRs) and enrichment in traits and biological pathways were assessed. A false discovery rate (FDR) < 0.1 and a genome-wide significance threshold of p < 9 × 10 -8 were used to control for false-positive results. The CpG cg12835256 ( PLA2G12A ) was genome-wide associated with FeNO in blood samples (coefficient= -0.015, p = 2.53 × 10 -9 ) and nominally associated in nasal samples (coefficient = -0.015, p = 0.045). Additionally, three CpGs were suggestively associated with BDR (FDR < 0.1). We identified 12 and four DMRs associated with FeNO and BDR (FDR < 0.05), respectively. An enrichment in allergic and inflammatory processes, smoking, and aging was observed. We reported novel associations of DNAm markers associated with BDR and FeNO enriched in asthma-related processes.
Databáze: MEDLINE