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Science Advances ISSN 2375-2548.
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Keywords :
Algorithms; Alleles; Computational Biology/methods; Gene Expression Regulation; Genetic Loci; Genome-Wide Association Study; Glycosylation; Humans; Immunoglobulin G/immunology/metabolism; Inflammation/genetics/metabolism; Linkage Disequilibrium; Models, Genetic; Phenotype; Polymorphism, Single Nucleotide; Polysaccharides/metabolism
Abstract :
[en] 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.
Publisher :
American Association for the Advancement of Science (AAAS), Washington, United States - District of Columbia
Commentary :
Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).
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