Home Medizin Studie kartiert das Gennetzwerk, das den komplexen Prozess der IgG-Glykosylierung im Alter steuert

Studie kartiert das Gennetzwerk, das den komplexen Prozess der IgG-Glykosylierung im Alter steuert

von NFI Redaktion

A new research paper was published in Altern (listed as „Aging (Albany NY)“ by MEDLINE/PubMed and „Aging-US“ by Web of Science) Volume 15, Issue 24, titled „Mapping the gene network regulating the glycan clock of aging.“

Glycans are an essential structural component of immunoglobulin G (IgG), which modulates its structure and function. However, the regulatory mechanisms behind this complex post-translational modification are not precisely known. Previous genome-wide association studies (GWAS) identified 29 genome regions involved in regulating IgG glycosylation, but few have been functionally validated. One of the key functional features of IgG glycosylation is the addition of galactose (galactosylation), a property that has been shown to be related to aging.

In this new study, researchers including Azra Frkatović-Hodžić, Anika Mijakovac, Karlo Miškec, Arina Nostaeva, Sodbo Z. Sharapov, Arianna Landini, Toomas Haller, Erik van den Akker, Sapna Sharma, Rafael RC Cuadrat, Massimo Mangino, Yong Li, Toma Keser, Najda Rudman, Tamara Štambuk, Maja Pučić-Baković, Irena Trbojević-Akmačić, Ivan Gudelj, Jerko Štambuk, Tea Pribić, Barbara Radovani, Petra Tominac, Krista Fischer, Marian Beekman, Manfred Wuhrer, Christian Gieger, Matthias B. Schulze, Clemens Wittenbecher, Ozren Polasek, Caroline Hayward, James F. Wilson, Tim D. Spector, Anna Köttgen, Frano Vučković, Yurii S. Aulchenko, Aleksandar Vojta, Jasminka Krištić, Lucija Klarić, and Vlatka Zoldoš from the Genos Glycoscience Research Laboratory, University of Zagreb, Novosibirsk State University, Lomonosov Moscow State University, University of Edinburgh, University of Tartu, Leiden University Medical Center, Delft University of Technology, Helmholtz Zentrum München, German Center for Diabetes Research (DZD), King’s College London, Guy’s and St Thomas‘ Foundation Trust, University of Freiburg, University of Rijeka, German Institute of Human Nutrition Potsdam-Rehbrücke, University of Potsdam, Harvard TH Chan School of Public Health, Chalmers University of Technology, University of Split School of Medicine, Algebra University College, Johns Hopkins Bloomberg School of Public Health, and Institute of Cytology and Genetics, SB RAS, conducted a GWAS of IgG galactosylation (N=13,705) and identified 16 significantly associated loci, suggesting that IgG galactosylation is regulated by a complex network of genes beyond the enzyme galactosyltransferase, which adds galactose to IgG glycans.

„Here, we conducted a GWAS of IgG galactosylation phenotypes in a study that almost doubled the sample size (N=13,705) compared to previous GWAS of IgG N-glycomes,“ said the researchers, who focused on genes with in silico evidence of involvement in the IgG galactosylation process.

Through gene prioritization, 37 candidate genes were identified. Using a recently developed CRISPR/dCas9 system, the researchers manipulated the gene expression of candidate genes in an in vitro IgG expression system. Upregulation of the three genes EEF1A1, MANBA, and TNFRSF13B altered the composition of the IgG glycome, confirming that these three genes are involved in IgG galactosylation in an in vitro expression system.

„Further investigations are needed to fully understand the functional mechanism behind their role in aging and to uncover the complete network of gene interactions regulating the complex process of IgG glycosylation,“ added the researchers.

Source:

Journal Reference:

Frkatović, A., et al. (2023). Mapping the gene network regulating the glycan clock of aging. Altern. doi.org/10.18632/aging.205106.

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