IgG glycosylation and DNA methylation are interconnected with smoking |
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| Authors: | Annika Wahl Silva Kasela Elena Carnero-Montoro Maarten van Iterson Jerko Štambuk Sapna Sharma Erik van den Akker Lucija Klaric Elisa Benedetti Genadij Razdorov Irena Trbojević-Akmačić Frano Vučković Ivo Ugrina Marian Beekman Joris Deelen Diana van Heemst Bastiaan T Heijmans Christian Gieger |
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| Institution: | 1. Research Unit Molecular Epidemiology, Institute of Epidemiology 2, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany;2. Institute of Epidemiology 2, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany;3. Estonian Genome Center, University of Tartu, Tartu, Estonia;4. Department of Twin Research and Genetic Epidemiology, King''s College London, London, UK;5. Department of Molecular Epidemiology, Leiden University Medical Center (LUMC), Leiden, The Netherlands;6. Genos Glycoscience Research Laboratory, Zagreb, Croatia;7. Pattern Recognition & Bioinformatics, Delft University of Technology, Delft, The Netherlands;8. Centre for Population Health Sciences, School of Molecular, Genetic and Population Health Sciences, University of Edinburgh, Edinburgh, United Kingdom;9. MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom;10. Institute of Computational Biology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany;11. University of Zagreb, Faculty of Pharmacy and Biochemistry, Zagreb, Croatia;12. University of Split, Faculty of Science, Split, Croatia;13. Center for Proteomics & Metabolomics, Leiden University Medical Center (LUMC), Leiden, The Netherlands;14. Max Planck Institute for Biology of Ageing, Köln, Germany;15. Department of Internal Medicine, Section Gerontology and Geriatrics, Leiden University Medical Center (LUMC), Leiden, The Netherlands;p. Biobank-Based Integrative Omics Study (BIOS) Consortium, The Netherlands;q. German Center for Diabetes Research (DZD), Neuherberg, Germany |
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| Abstract: | BackgroundGlycosylation is one of the most common post-translation modifications with large influences on protein structure and function. The effector function of immunoglobulin G (IgG) alters between pro- and anti-inflammatory, based on its glycosylation. IgG glycan synthesis is highly complex and dynamic.MethodsWith the use of two different analytical methods for assessing IgG glycosylation, we aim to elucidate the link between DNA methylation and glycosylation of IgG by means of epigenome-wide association studies. In total, 3000 individuals from 4 cohorts were analyzed.ResultsThe overlap of the results from the two glycan measurement panels yielded DNA methylation of 7 CpG-sites on 5 genomic locations to be associated with IgG glycosylation: cg25189904 (chr.1, GNG12); cg05951221, cg21566642 and cg01940273 (chr.2, ALPPL2); cg05575921 (chr.5, AHRR); cg06126421 (6p21.33); and cg03636183 (chr.19, F2RL3). Mediation analyses with respect to smoking revealed that the effect of smoking on IgG glycosylation may be at least partially mediated via DNA methylation levels at these 7 CpG-sites.ConclusionOur results suggest the presence of an indirect link between DNA methylation and IgG glycosylation that may in part capture environmental exposures.General significanceAn epigenome-wide analysis conducted in four population-based cohorts revealed an association between DNA methylation and IgG glycosylation patterns. Presumably, DNA methylation mediates the effect of smoking on IgG glycosylation. |
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| Keywords: | DNA methylation IgG glycosylation Smoking EWAS Mediation |
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