GLI2 promoter hypermethylation in saliva of children with a respiratory allergy

Sabine A S Langie, Matthieu Moisse, Katarzyna Szarc Vel Szic, Ellen Van Der Plas, Gudrun Koppen, Sofie De Prins, Tijs Louwies, Vera Nelen, Guy Van Camp, Diether Lambrechts, Greet Schoeters, Wim Vanden Berghe, Patrick De Boever

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Resumé

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.

OriginalsprogEngelsk
Artikelnummer50
TidsskriftClinical Epigenetics (Print)
Vol/bind10
Antal sider13
ISSN1868-7075
DOI
StatusUdgivet - 11. apr. 2018

Fingeraftryk

Saliva
Hypersensitivity
DNA Methylation
Genetic Markers
Epigenomics
Lung

Citer dette

Langie, S. A. S., Moisse, M., Szarc Vel Szic, K., Van Der Plas, E., Koppen, G., De Prins, S., ... De Boever, P. (2018). GLI2 promoter hypermethylation in saliva of children with a respiratory allergy. Clinical Epigenetics (Print), 10, [50]. https://doi.org/10.1186/s13148-018-0484-1
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. I: Clinical Epigenetics (Print). 2018 ; Bind 10.
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title = "GLI2 promoter hypermethylation in saliva of children with a respiratory allergy",
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.",
keywords = "DNA methylation, GLI2, Illumina Methylation 450K BeadChip, Respiratory allergy, Saliva, Promoter Regions, Genetic, Genome-Wide Association Study, Epigenesis, Genetic, Humans, Child, Preschool, Male, Zinc Finger Protein Gli2/genetics, Saliva/chemistry, Case-Control Studies, Respiratory Hypersensitivity/genetics, DNA Methylation, Belgium, CpG Islands, Female, Nuclear Proteins/genetics, Child, Longitudinal Studies",
author = "Langie, {Sabine A S} and Matthieu Moisse and {Szarc Vel Szic}, Katarzyna and {Van Der Plas}, Ellen and Gudrun Koppen and {De Prins}, Sofie and Tijs Louwies and Vera Nelen and {Van Camp}, Guy and Diether Lambrechts and Greet Schoeters and {Vanden Berghe}, Wim and {De Boever}, Patrick",
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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 & De Boever, P 2018, 'GLI2 promoter hypermethylation in saliva of children with a respiratory allergy', Clinical Epigenetics (Print), bind 10, 50. https://doi.org/10.1186/s13148-018-0484-1

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.

I: Clinical Epigenetics (Print), Bind 10, 50, 11.04.2018.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - GLI2 promoter hypermethylation in saliva of children with a respiratory allergy

AU - Langie, Sabine A S

AU - Moisse, Matthieu

AU - Szarc Vel Szic, Katarzyna

AU - Van Der Plas, Ellen

AU - Koppen, Gudrun

AU - De Prins, Sofie

AU - Louwies, Tijs

AU - Nelen, Vera

AU - Van Camp, Guy

AU - Lambrechts, Diether

AU - Schoeters, Greet

AU - Vanden Berghe, Wim

AU - De Boever, Patrick

PY - 2018/4/11

Y1 - 2018/4/11

N2 - 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.

AB - 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.

KW - DNA methylation

KW - GLI2

KW - Illumina Methylation 450K BeadChip

KW - Respiratory allergy

KW - Saliva

KW - Promoter Regions, Genetic

KW - Genome-Wide Association Study

KW - Epigenesis, Genetic

KW - Humans

KW - Child, Preschool

KW - Male

KW - Zinc Finger Protein Gli2/genetics

KW - Saliva/chemistry

KW - Case-Control Studies

KW - Respiratory Hypersensitivity/genetics

KW - DNA Methylation

KW - Belgium

KW - CpG Islands

KW - Female

KW - Nuclear Proteins/genetics

KW - Child

KW - Longitudinal Studies

U2 - 10.1186/s13148-018-0484-1

DO - 10.1186/s13148-018-0484-1

M3 - Journal article

C2 - 29682088

VL - 10

JO - Clinical Epigenetics (Print)

JF - Clinical Epigenetics (Print)

SN - 1868-7075

M1 - 50

ER -

Langie SAS, Moisse M, Szarc Vel Szic K, Van Der Plas E, Koppen G, De Prins S et al. GLI2 promoter hypermethylation in saliva of children with a respiratory allergy. Clinical Epigenetics (Print). 2018 apr 11;10. 50. https://doi.org/10.1186/s13148-018-0484-1