1. GLI2 promoter hypermethylation in saliva of children with a respiratory allergy.
- Author
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Langie SAS, Moisse M, Szarc Vel Szic K, Van Der Plas E, Koppen G, De Prins S, Louwies T, Nelen V, Van Camp G, Lambrechts D, Schoeters G, Vanden Berghe W, and De Boever P
- Subjects
- Belgium, Case-Control Studies, Child, Child, Preschool, CpG Islands, Epigenesis, Genetic, Female, Genome-Wide Association Study, Humans, Longitudinal Studies, Male, Promoter Regions, Genetic, DNA Methylation, Nuclear Proteins genetics, Respiratory Hypersensitivity genetics, Saliva chemistry, Zinc Finger Protein Gli2 genetics
- Abstract
Background: The prevalence of respiratory allergy in children is increasing. Epigenetic DNA methylation changes are plausible underlying molecular mechanisms., Results: Saliva samples collected in substudies of two longitudinal birth cohorts in Belgium (FLEHS1 & FLEHS2) were used to discover and confirm DNA methylation signatures that can differentiate individuals with respiratory allergy from healthy subjects. Genome-wide analysis with Illumina Methylation 450K BeadChips revealed 23 differentially methylated gene regions (DMRs) in saliva from 11y old allergic children (N=26) vs. controls (N=20) in FLEHS1. A subset of 7 DMRs was selected for confirmation by iPLEX MassArray analysis. First, iPLEX analysis was performed in the same 46 FLEHS1 samples for analytical confirmation of the findings obtained during the discovery phase. iPLEX results correlated significantly with the 450K array data ( P <0.0001) and confirmed 4 out of the 7 DMRs. Aiming for additional biological confirmation, the 7 DMRs were analyzed using iPLEX in a substudy of an independent birth cohort (FLEHS2; N=19 cases vs. 20 controls, aged 5 years). One DMR in the GLI2 promoter region showed a consistent statistically significant hypermethylation in individuals with respiratory allergy across the two birth cohorts and technologies. In addition to its involvement in TGF-β signaling and T-helper differentiation, GLI2 has a regulating role in lung development., Conclusion: GLI2 is considered an interesting candidate DNA methylation marker for respiratory allergy., Competing Interests: The follow-up studies of both campaigns were approved by the ethical committee of the University of Antwerp (B300201317947), and parents signed the informed consent on behalf of the children.Not applicable.In relation to this work, VITO applied for the patent “RESPIRATORY ALLERGY - Allergim-1,” which was published on 8/12/2016 (WO 2016/193151 A1).Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
- Published
- 2018
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