Martin-Almeida, Mario and Perez-Garcia, Javier and Herrera-Luis, Esther and Rosa-Baez, Carlos and Gorenjak, Mario and Neerincx, Anne H. and Sardon-Prado, Olaia and Toncheva, Antoaneta A. and Harner, Susanne and Wolff, Christine and Brandstetter, Susanne and Valletta, Elisa and Abdel-Aziz, Mahmoud and Hashimoto, Simone and Berce, Vojko and Corcuera-Elosegui, Paula and Korta-Murua, Javier and Buntrock-Doepke, Heike and Vijverberg, Susanne J. H. and Verster, Joris C. and Kerssemakers, Nikki and Hedman, Anna M. and Almqvist, Catarina and Villar, Jesus and Kraneveld, Aletta D. and Potocnik, Uros and Kabesch, Michael and Maitland-van der Zee, Anke H. and Pino-Yanes, Maria (2023) Epigenome-Wide Association Studies of the Fractional Exhaled Nitric Oxide and Bronchodilator Drug Response in Moderate-to-Severe Pediatric Asthma. BIOMEDICINES, 11 (3): 676. ISSN , 2227-9059
Full text not available from this repository. (Request a copy)Abstract
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 x 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 x 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | AIRWAY RESPONSIVENESS; IMMUNOGLOBULIN-E; METHYLATION; PATHWAY; IL-6; SET; epigenetic; biomarker; methylation; asthma; FeNO; BDR; precision medicine |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Kinder- und Jugendmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 09 Apr 2024 07:02 |
| Last Modified: | 09 Apr 2024 07:02 |
| URI: | https://pred.uni-regensburg.de/id/eprint/60731 |
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