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Farm exposure and time trends in early childhood may influence DNA methylation in genes related to asthma and allergy

Michel, S. and Busato, F. and Genuneit, J. and Pekkanen, J. and Dalphin, J. C. and Riedler, J. and Mazaleyrat, N. and Weber, J. and Karvonen, A. M. and Hirvonen, M. R. and Braun-Fahrländer, C. and Lauener, R. and von Mutius, E. and Kabesch, M. and Tost, J.. (2013) Farm exposure and time trends in early childhood may influence DNA methylation in genes related to asthma and allergy. Allergy : european journal of allergy and clinical immunology : official journal of the European Academy of Allergology and Clinical Immunology, Vol. 68, H. 3. pp. 355-364.

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Official URL: http://edoc.unibas.ch/dok/A6124621

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Abstract

BACKGROUND: Genetic susceptibility and environmental influences are important contributors to the development of asthma and atopic diseases. Epigenetic mechanisms may facilitate gene by environment interactions in these diseases. METHODS: We studied the rural birth cohort PASTURE (Protection against allergy: study in rural environments) to investigate (a) whether epigenetic patterns in asthma candidate genes are influenced by farm exposure in general, (b) change over the first years of life, and (c) whether these changes may contribute to the development of asthma. DNA was extracted from cord blood and whole blood collected at the age of 4.5 years in 46 samples per time point. DNA methylation in 23 regions in ten candidate genes (ORMDL1, ORMDL2, ORMDL3, CHI3L1, RAD50, IL13, IL4, STAT6, FOXP3, and RUNX3) was assessed by pyrosequencing, and differences between strata were analyzed by nonparametric Wilcoxon-Mann-Whitney tests. RESULTS: In cord blood, regions in ORMDL1 and STAT6 were hypomethylated in DNA from farmers' as compared to nonfarmers' children, while regions in RAD50 and IL13 were hypermethylated (lowest P-value (STAT6) = 0.001). Changes in methylation over time occurred in 15 gene regions (lowest P-value (IL13) = 1.57*10(-8) ). Interestingly, these differences clustered in the genes highly associated with asthma (ORMDL family) and IgE regulation (RAD50, IL13, and IL4), but not in the T-regulatory genes (FOXP3, RUNX3). CONCLUSIONS: In this first pilot study, DNA methylation patterns change significantly in early childhood in specific asthma- and allergy-related genes in peripheral blood cells, and early exposure to farm environment seems to influence methylation patterns in distinct genes
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Former Units within Swiss TPH > Microbial Exposure & Childhood Allergies (Braun-Fahrländer)
UniBasel Contributors:Braun-Fahrländer, Charlotte
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Munksgaard
ISSN:0105-4538
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:16 Aug 2013 07:34
Deposited On:16 Aug 2013 07:30

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