Farm exposure and time trends in early childhood may influence DNA methylation in genes related to asthma and allergy. Issue 3 (25th January 2013)

• Record Type: Journal Article
• Authors: Michel, S.; Busato, F.; Genuneit, J.; Pekkanen, J.; Dalphin, J.‐C.; Riedler, J.; Mazaleyrat, N.; Weber, J.; Karvonen, A. M.; Hirvonen, M.‐R.; Braun‐Fahrländer, C.; Lauener, R.; von, E.; Kabesch, M.; Tost, J.
• Is Part Of: Allergy. Volume 68:Issue 3(2013:Mar.)
• Page Start: 355
• Page End: 364
• Publication Date: 2013-01-25
• Subjects: Allergy -- Periodicals; 616.97
• DOI: 10.1111/all.12097
• Languages: English
• ISSNs: 0105-4538

Abstract

<abstract abstract-type="main" id="all12097-abs-0001"> <title>Abstract</title> <sec id="all12097-sec-0001" sec-type="section"> <title>Background</title> <p>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.</p> </sec> <sec id="all12097-sec-0002" sec-type="section"> <title>Methods</title> <p>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 (<italic>ORMDL1</italic>, <italic> ORMDL2</italic>, <italic> ORMDL3</italic>, <italic> CHI3L1</italic>, <italic> RAD50</italic>, <italic> IL13, IL4</italic>, <italic> STAT6</italic>, <italic> FOXP3, </italic> and <italic>RUNX3</italic>) was assessed by pyrosequencing, and differences between strata were analyzed by nonparametric Wilcoxon–Mann–Whitney tests.</p> </sec> <sec id="all12097-sec-0003" sec-type="section"> <title>Results</title> <p>In cord blood, regions in <italic>ORMDL1</italic> and <italic>STAT6</italic> were hypomethylated in DNA from farmers' as compared to nonfarmers' children, while regions in <italic>RAD50</italic> and <italic>IL13</italic> were hypermethylated (lowest <italic>P</italic>‐value (<italic>STAT6</italic>) = 0.001). Changes in methylation over time occurred in 15 gene regions (lowest <italic>P</italic>‐value (<italic>IL13</italic>) = 1.57*10<sup>−8</sup>). Interestingly, these differences clustered in the genes highly associated with asthma (<italic>ORMDL</italic> family) and IgE regulation (<italic>RAD50</italic>, <italic> IL13, </italic> and <italic>IL4</italic>), but not in the T‐regulatory genes (<italic>FOXP3</italic>, <italic> RUNX3</italic>).</p> </sec> <sec id="all12097-sec-0004" sec-type="section"> <title>Conclusions</title> <p>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.</p> </sec> </abstract>