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Biochim Biophys Acta Gen Subj. 2018 Mar;1862(3):637-648. doi: 10.1016/j.bbagen.2017.10.012. Epub 2017 Oct 18.

IgG glycosylation and DNA methylation are interconnected with smoking.

Author information

1
Research Unit Molecular Epidemiology, Institute of Epidemiology 2, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany; Institute of Epidemiology 2, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
2
Estonian Genome Center, University of Tartu, Tartu, Estonia.
3
Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
4
Department of Molecular Epidemiology, Leiden University Medical Center (LUMC), Leiden, The Netherlands.
5
Genos Glycoscience Research Laboratory, Zagreb, Croatia.
6
Department of Molecular Epidemiology, Leiden University Medical Center (LUMC), Leiden, The Netherlands; Pattern Recognition & Bioinformatics, Delft University of Technology, Delft, The Netherlands.
7
Genos Glycoscience Research Laboratory, Zagreb, Croatia; Centre for Population Health Sciences, School of Molecular, Genetic and Population Health Sciences, University of Edinburgh, Edinburgh, United Kingdom; MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
8
Institute of Computational Biology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
9
University of Zagreb, Faculty of Pharmacy and Biochemistry, Zagreb, Croatia; University of Split, Faculty of Science, Split, Croatia.
10
Department of Molecular Epidemiology, Leiden University Medical Center (LUMC), Leiden, The Netherlands; Max Planck Institute for Biology of Ageing, Köln, Germany.
11
Department of Internal Medicine, Section Gerontology and Geriatrics, Leiden University Medical Center (LUMC), Leiden, The Netherlands.
12
Biobank-Based Integrative Omics Study (BIOS) Consortium, The Netherlands.
13
Center for Proteomics & Metabolomics, Leiden University Medical Center (LUMC), Leiden, The Netherlands.
14
University of Zagreb, Faculty of Pharmacy and Biochemistry, Zagreb, Croatia.
15
Research Unit Molecular Epidemiology, Institute of Epidemiology 2, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany; Institute of Epidemiology 2, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany; German Center for Diabetes Research (DZD), Neuherberg, Germany.
16
Institute of Epidemiology 2, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
17
Genos Glycoscience Research Laboratory, Zagreb, Croatia; University of Zagreb, Faculty of Pharmacy and Biochemistry, Zagreb, Croatia.
18
Research Unit Molecular Epidemiology, Institute of Epidemiology 2, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany; Institute of Epidemiology 2, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany. Electronic address: christian.gieger@helmholtz-muenchen.de.

Abstract

BACKGROUND:

Glycosylation 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.

METHODS:

With 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.

RESULTS:

The 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.

CONCLUSION:

Our results suggest the presence of an indirect link between DNA methylation and IgG glycosylation that may in part capture environmental exposures.

GENERAL SIGNIFICANCE:

An 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.

KEYWORDS:

DNA methylation; EWAS; IgG glycosylation; Mediation; Smoking

PMID:
29055820
DOI:
10.1016/j.bbagen.2017.10.012
[Indexed for MEDLINE]
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