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Frkatović-Hodžić, A.* ; Mijakovac, A.* ; Miškec, K.* ; Nostaeva, A.* ; Sharapov, S.Z.* ; Landini, A.* ; Haller, T.* ; Akker, E.V.D.* ; Sharma, S. ; Cuadrat, R.R.C. ; Mangino, M.* ; Li, Y.* ; Keser, T.* ; Rudman, N.* ; Štambuk, T.* ; Pučić-Baković, M.* ; Trbojević-Akmačić, I.* ; Gudelj, I.* ; Štambuk, J.* ; Pribić, T.* ; Radovani, B.* ; Tominac, P.* ; Fischer, K.* ; Beekman, M.* ; Wuhrer, M.* ; Gieger, C. ; Schulze, M.B.* ; Wittenbecher, C.* ; Polasek, O.* ; Hayward, C.* ; Wilson, J.F.* ; Spector, T.D.* ; Köttgen, A.* ; Vučković, F.* ; Aulchenko, Y.S.* ; Vojta, A.* ; Krištić, J.* ; Klarić, L.* ; Zoldoš, V.* ; Lauc, G.*

Mapping of the gene network that regulates glycan clock of ageing.

Aging 15, 14509-14552 (2023)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Glycans are an essential structural component of immunoglobulin G (IgG) that modulate its structure and function. However, regulatory mechanisms behind this complex posttranslational modification are not well known. Previous genome-wide association studies (GWAS) identified 29 genomic regions involved in regulation of IgG glycosylation, but only a few were functionally validated. One of the key functional features of IgG glycosylation is the addition of galactose (galactosylation), a trait which was shown to be associated with ageing. We performed GWAS of IgG galactosylation (N=13,705) and identified 16 significantly associated loci, indicating that IgG galactosylation is regulated by a complex network of genes that extends beyond the galactosyltransferase enzyme that adds galactose to IgG glycans. Gene prioritization identified 37 candidate genes. Using a recently developed CRISPR/dCas9 system we manipulated gene expression of candidate genes in the in vitro IgG expression system. Upregulation of three genes, EEF1A1, MANBA and TNFRSF13B, changed the IgG glycome composition, which confirmed that these three genes are involved in IgG galactosylation in this in vitro expression system.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Crispr/dcas9 ; Genome-wide Association Study ; Glycan Clock ; Glycosylation ; Immunoglobulin G
Sprache englisch
Veröffentlichungsjahr 2023
HGF-Berichtsjahr 2023
ISSN (print) / ISBN 1945-4589
e-ISSN 1945-4589
Zeitschrift Aging
Quellenangaben Band: 15, Heft: 24, Seiten: 14509-14552 Artikelnummer: , Supplement: ,
Verlag Impact Journals LLC
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Epidemiology (EPI)
POF Topic(s) 30202 - Environmental Health
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-504091-002
G-504091-004
DOI 10.18632/aging.205106
WOS ID 001138232700026
Scopus ID 85181763900
PubMed ID 38149987
Erfassungsdatum 2024-01-07
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