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DNA methylation in asthma and allergy related genes is influenced by farm exposure and time trends in early childhood

Sven Michel, Florence Busato, Jon Genuneit, Juha Pekkanen, Charles Dalphin, Josef Riedler, Nicolas Mazaleyrat, Erika von Mutius, Juliane Weber, Charlotte Braun-Fahrländer, Roger Lauener, Michael Kabesch, Jörg Tost, the PASTURE study group
European Respiratory Journal 2012 40: 4714; DOI:
Sven Michel
1Department of Pediatric Pneumology, Allergy and Neonatology, Hannover Medical School, Hannover, Germany
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Florence Busato
2Laboratory for Epigenetics, Centre National de Génotypage, CEA–Institut de Génomique, Evry, France
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Jon Genuneit
3Institute of Epidemiology and Medical Biometry, Ulm University, Ulm, Germany
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Juha Pekkanen
4National Institute for Health and Welfare, THL Kuopio, Kuopio, Finland
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Charles Dalphin
5Department of Respiratory Disease, Université de Franche-Comté, Besancon, France
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Josef Riedler
6Children's Hospital Schwarzach, Children's Hospital Schwarzach, Schwarzach, Austria
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Nicolas Mazaleyrat
2Laboratory for Epigenetics, Centre National de Génotypage, CEA–Institut de Génomique, Evry, France
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Erika von Mutius
7University Children's Hospital, LMU, Munich, Germany
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Juliane Weber
7University Children's Hospital, LMU, Munich, Germany
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Charlotte Braun-Fahrländer
8Institute of Social and Preventive Medicine, Swiss Tropical and Public Health Institute, Basel, Switzerland
9University of Basel, University of Basel, Switzerland
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Roger Lauener
10Children's Hospital and Christine Kühne-Center for Allergy, University of Zürich, Switzerland
11Christine Kühne-Center for Allergy Research and Education, Hochgebirgsklinik Davos, Davos-Wolfgang, Switzerland
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Michael Kabesch
1Department of Pediatric Pneumology, Allergy and Neonatology, Hannover Medical School, Hannover, Germany
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Jörg Tost
2Laboratory for Epigenetics, Centre National de Génotypage, CEA–Institut de Génomique, Evry, France
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1Department of Pediatric Pneumology, Allergy and Neonatology, Hannover Medical School, Hannover, Germany
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Abstract

Genes and environmental influences are crucial for the development of asthma and atopic diseases. These factors may act upon each other through epigenetic mechanisms.

We studied the rural birth cohort PASTURE (Protection against allergy: study in rural environments) to investigate if (a) epigenetic patterns in asthma candidate genes are influenced by farm exposure in general and (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 at age 4.5 in 48 samples per time point. We analyzed DNA methylation of 23 regions in ten asthma and allergy candidate genes (ORMDL1, ORMDL2, ORMDL3, CHI3L1, RAD50, IL13, IL4, STAT6, FOXP3 and RUNX3) by pyrosequencing and compared differences between strata.

In cord blood, regions in ORMDL1 and STAT6 showed a hypomethylation while regions in RAD50 and IL13 were hypermethylated when DNA from farmers was compared to non-farmers (lowest p-value 0.001 for STAT6). Only small associations between asthma status and methylation were observed in our population. Changes in methylation over time occurred in 14 out of 23 gene regions investigated (lowest p-value for IL13, p=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).

Our study indicates that DNA methylation changes significantly in early childhood in specific asthma and allergy related genes in peripheral blood cells while also early exposure to farm life seems to influence methylation patterns in certain genes.

  • Epigenetics
  • Environment
  • © 2012 ERS
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DNA methylation in asthma and allergy related genes is influenced by farm exposure and time trends in early childhood
Sven Michel, Florence Busato, Jon Genuneit, Juha Pekkanen, Charles Dalphin, Josef Riedler, Nicolas Mazaleyrat, Erika von Mutius, Juliane Weber, Charlotte Braun-Fahrländer, Roger Lauener, Michael Kabesch, Jörg Tost, the PASTURE study group
European Respiratory Journal Sep 2012, 40 (Suppl 56) 4714;

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DNA methylation in asthma and allergy related genes is influenced by farm exposure and time trends in early childhood
Sven Michel, Florence Busato, Jon Genuneit, Juha Pekkanen, Charles Dalphin, Josef Riedler, Nicolas Mazaleyrat, Erika von Mutius, Juliane Weber, Charlotte Braun-Fahrländer, Roger Lauener, Michael Kabesch, Jörg Tost, the PASTURE study group
European Respiratory Journal Sep 2012, 40 (Suppl 56) 4714;
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