Glycosylation of immunoglobulin G is regulated by a large network of genes pleiotropic with inflammatory diseases.

Science Advances
Lucija KlarićCaroline Hayward

Abstract

Effector functions of immunoglobulin G (IgG) are regulated by the composition of a glycan moiety, thus affecting activity of the immune system. Aberrant glycosylation of IgG has been observed in many diseases, but little is understood about the underlying mechanisms. We performed a genome-wide association study of IgG N-glycosylation (N = 8090) and, using a data-driven network approach, suggested how associated loci form a functional network. We confirmed in vitro that knockdown of IKZF1 decreases the expression of fucosyltransferase FUT8, resulting in increased levels of fucosylated glycans, and suggest that RUNX1 and RUNX3, together with SMARCB1, regulate expression of glycosyltransferase MGAT3. We also show that variants affecting the expression of genes involved in the regulation of glycoenzymes colocalize with variants affecting risk for inflammatory diseases. This study provides new evidence that variation in key transcription factors coupled with regulatory variation in glycogenes modifies IgG glycosylation and has influence on inflammatory diseases.

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Citations

Jun 21, 2020·Proceedings of the National Academy of Sciences of the United States of America·Sem TamaraAlbert J R Heck
Aug 31, 2020·Molecular Aspects of Medicine·Tamara ŠtambukGordan Lauc
Jan 26, 2021·Journal of Diabetes·Zhiyuan WuXiuhua Guo
Dec 12, 2020·Cancer Prevention Research·Zhiyuan WuXiuhua Guo
Apr 27, 2021·Frontiers in Pharmacology·Riccardo CapecchiLorenzo Bertani
Oct 12, 2021·Frontiers in Immunology·Haifeng HouWei Wang

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Datasets Mentioned

BETA
GM12878

Methods Mentioned

BETA
glycosylation
gene knockout
immunoprecipitation
ChIP
Hi-C
ChIP-seq
PCR
electrophoresis

Software Mentioned

Cytoscape
Expression Prioritized Integration for Complex Traits ( DEPICT )
FUMA GENE2FUNC
GraphPad QuickCalcs
- RNAi Designer
FUMA
sva
R
EasyQC
- COJO analysis

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