IgG glycosylation and DNA methylation are interconnected with smoking

Annika Wahl, Silva Kasela, Elena Carnero Monotoro, 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, B I O S Consortium, Manfred Wuhrer, Rosina PlompToma Keser, Mirna Šimurina, Tamara Pavić, Ivan Gudelj, Jasminka Krištić, Harald Grallert, Sonja Kunze, Annette Peters, Jordana T Bell, Timothy D Spector, Lili Milani, P Eline Slagboom, Gordan Lauc, Christian Gieger

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
JournalBBA - Bioenergetics
Early online date18 Oct 2017
DOIs
Publication statusE-pub ahead of print - 18 Oct 2017

Keywords

  • Journal Article

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