Increased vitamin D levels at birth and in early infancy increase offspring allergy risk— evidence for involvement of epigenetic mechanisms Kristin M.

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Increased vitamin D levels at birth and in early infancy increase offspring allergy risk— evidence for involvement of epigenetic mechanisms Kristin M. Junge, PhD, Tobias Bauer, PhD, Stefanie Geissler, PhD, Frank Hirche, PhD, Loreen Thürmann, MSc, Mario Bauer, MD, Saskia Trump, PhD, Matthias Bieg, MSc, Dieter Weichenhan, PhD, Lei Gu, PhD, Jan-Philipp Mallm, PhD, Naveed Ishaque, PhD, Oliver Mücke, Stefan Röder, PhD, Gunda Herberth, PhD, Ulrike Diez, MD, Michael Borte, MD, Karsten Rippe, PhD, Christoph Plass, PhD, Carl Hermann, PhD, Gabriele I. Stangl, PhD, Roland Eils, PhD, Irina Lehmann, PhD Journal of Allergy and Clinical Immunology Volume 137, Issue 2, Pages 610-613 (February 2016) DOI: 10.1016/j.jaci.2015.06.040 Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 TSLP DMR, histone marks, and mRNA expression. A, Location of the TSLP DMR in relation to the TSLP gene (upper part). The TSLP DMR shows a predicted chromosomal interaction with the TSLP promoter (red bar). Furthermore, chromatin segmentation tracks generated by ChromHMM are displayed for 2 (high cord blood 25[OH]D3) vs 2 (low cord blood 25[OH]D3) samples over the region relating to the DMR and TSLP gene (upper part), and a close-up of the DMR region (lower part): Repressed chromatin states are observed in samples of low 25(OH)D3 (blue bars) over the DMR region, and an ECNODE-predicted weak enhancer is found nearby (WE; black bar; lower part of the Fig 1, A). B, Association between TSLP enhancer methylation at birth (mean of 2 CpGs at Chr5:110.292.389-392, which marks the start of the enhancer region close to the TSLP DMR; analyzed via MassARRAY) and cord blood 25(OH)D3; shown for all participants (left column), only for those within the high vitamin D group (25[OH]D3 >75th percentile, middle column), or for those within the low vitamin D group (25[OH]D3 <25th percentile, right column). C, Association between methylation of the TSLP enhancer region (2 CpGs at Chr5:110.292.389-392) and TSLP mRNA expression, both analyzed in cord blood. D, Association between cord blood TSLP mRNA expression and 25(OH)D3 concentrations. E, Association between TSLP mRNA expression at year 1 (first year) and cord blood 25(OH)D3 concentration. F, TSLP mRNA expression at year 1 (first year) in children with (yes) or without (no) wheezing symptoms ever within the third year of life (P values from Mann-Whitney U test). Journal of Allergy and Clinical Immunology 2016 137, 610-613DOI: (10.1016/j.jaci.2015.06.040) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions