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

Authors: Lucija Klarić, Yakov A. Tsepilov, Chloë M. Stanton, Massimo Mangino, Timo Tõnis Sikka, Tõnu Esko, Eugene Pakhomov, Perttu Salo, Joris Deelen, Stuart J. McGurnaghan, Toma Keser, Frano Vučković, Ivo Ugrina, Jasminka Krištić, Ivan Gudelj, Jerko Štambuk, Rosina Plomp, Maja Pučić‐Baković, Tamara Pavić, Marija Vilaj, Irena Trbojević‐Akmačić, Camilla Drake, Paula Dobrinić, Jelena Mlinarec, Barbara Jelušić, Anne Richmond, Maria Timofeeva, Alexander K. Grishchenko, Julia Dmitrieva, Mairead L. Bermingham, Sodbo Sharapov, Susan M. Farrington, Evropi Τheodoratou, Hae‐Won Uh, Marian Beekman, P. Eline Slagboom, Édouard Louis, Michel Georges, Manfred Wuhrer, Helen M. Colhoun, Malcolm G. Dunlop, Markus Perola, Krista Fischer, Ozren Polašek, Harry Campbell, Igor Rudan, James F. Wilson, Vlatka Zoldoš, Véronique Vitart, Tim D. Spector, Yurii S. Aulchenko, Gordan Lauc, Caroline Hayward - Science Advances 2020 cited by 139

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.