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GLI2 promoter hypermethylation in saliva of children with a respiratory allergy
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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5896137/ https://www.ncbi.nlm.nih.gov/pubmed/29682088 http://dx.doi.org/10.1186/s13148-018-0484-1 |
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author | Langie, Sabine A. S. Moisse, Matthieu Szarc vel Szic, Katarzyna Van Der Plas, Ellen Koppen, Gudrun De Prins, Sofie Louwies, Tijs Nelen, Vera Van Camp, Guy Lambrechts, Diether Schoeters, Greet Vanden Berghe, Wim De Boever, Patrick |
author_facet | Langie, Sabine A. S. Moisse, Matthieu Szarc vel Szic, Katarzyna Van Der Plas, Ellen Koppen, Gudrun De Prins, Sofie Louwies, Tijs Nelen, Vera Van Camp, Guy Lambrechts, Diether Schoeters, Greet Vanden Berghe, Wim De Boever, Patrick |
author_sort | Langie, Sabine A. S. |
collection | PubMed |
description | 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13148-018-0484-1) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5896137 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-58961372018-04-20 GLI2 promoter hypermethylation in saliva of children with a respiratory allergy Langie, Sabine A. S. Moisse, Matthieu Szarc vel Szic, Katarzyna Van Der Plas, Ellen Koppen, Gudrun De Prins, Sofie Louwies, Tijs Nelen, Vera Van Camp, Guy Lambrechts, Diether Schoeters, Greet Vanden Berghe, Wim De Boever, Patrick Clin Epigenetics Research 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13148-018-0484-1) contains supplementary material, which is available to authorized users. BioMed Central 2018-04-11 /pmc/articles/PMC5896137/ /pubmed/29682088 http://dx.doi.org/10.1186/s13148-018-0484-1 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Langie, Sabine A. S. Moisse, Matthieu Szarc vel Szic, Katarzyna Van Der Plas, Ellen Koppen, Gudrun De Prins, Sofie Louwies, Tijs Nelen, Vera Van Camp, Guy Lambrechts, Diether Schoeters, Greet Vanden Berghe, Wim De Boever, Patrick GLI2 promoter hypermethylation in saliva of children with a respiratory allergy |
title | GLI2 promoter hypermethylation in saliva of children with a respiratory allergy |
title_full | GLI2 promoter hypermethylation in saliva of children with a respiratory allergy |
title_fullStr | GLI2 promoter hypermethylation in saliva of children with a respiratory allergy |
title_full_unstemmed | GLI2 promoter hypermethylation in saliva of children with a respiratory allergy |
title_short | GLI2 promoter hypermethylation in saliva of children with a respiratory allergy |
title_sort | gli2 promoter hypermethylation in saliva of children with a respiratory allergy |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5896137/ https://www.ncbi.nlm.nih.gov/pubmed/29682088 http://dx.doi.org/10.1186/s13148-018-0484-1 |
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