MGAT3 gene promoter methylation correlates with IgG glycosylation in inflammatory bowel disease (IBD) (CROSBI ID 647561)
Prilog sa skupa u zborniku | sažetak izlaganja sa skupa | međunarodna recenzija
Podaci o odgovornosti
Vojta, Aleksandar ; Markulin, Dora ; Klasić, Marija ; Trbojević-Akmačić, Irena ; Lauc, Gordan ; Zoldoš, Vlatka
engleski
MGAT3 gene promoter methylation correlates with IgG glycosylation in inflammatory bowel disease (IBD)
Inflammatory bowel diseases (IBD) represent a group of intestinal disorders that occur due to inappropriate immune response to intestinal microbiome in genetically susceptible individuals. Genome-wide association studies found a connection between the MGAT3 and BACH2 genes, IgG glycosylation and IBD. We analyzed methylation of MGAT3 and BACH2 gene promoters from whole blood of IBD patients from two large independent cohorts using bisulfite pyrosequencing. Promoter methylation, taken as a putative regulation mechanism for expression of MGAT3 and BACH2, was correlated to glycan structures found on IgG molecules from the same blood samples. Significant correlations were found between MGAT3 promoter methylation and the FA2B/FA2 ratio, suggesting that activity of the GnT-III enzyme, which is encoded by the MGAT3 gene, might be altered in IBD. In line with this, FA2 was positively correlated with MGAT3 promoter methylation, suggesting that the substrate abundance decreases when the enzyme is more actively transcribed due to decreased methylation. However, it is still unclear whether the CpG sites analyzed in our methylation assays are directly involved in transcriptional regulation, or they merely reflect the overall methylation of the promoter region. Another significant correlation was found between the MGAT3 promoter methylation and galactosylated and sialylated structures. It appears as though these processes are co- regulated with MGAT3 expression. This effect has been observed in other unrelated studies ; however, there is no straightforward explanation. Taken together, the effects of MGAT3 promoter methylation on IgG glycans in IBD suggest its potential as a biomarker or even a therapeutic target. Methylation of BACH2, a putative regulator of IgG glycosylation, was not significantly and/or reproducibly correlated with glycan structures. While this does not necessarily rule out its role in IgG glycosylation, its effect is then probably complex and tightly interrelated with other factors influencing the glycosylation pathway.
IBD, MGAT3 ; correlation ; CpG methylation ; glycosylation
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Podaci o prilogu
114-115.
2017.
objavljeno
Podaci o matičnoj publikaciji
12th Jenner Glycobiology and Medicine Symposium, Translational Glycobiology, From Bench to Bedside: PROGRAMME BOOK / BOOK OF ABSTRACTS
Podaci o skupu
12th Jenner Glycobiology and Medicine Symposium - Translational Glycobiology, From Bench to Bedside
poster
06.05.2017-09.05.2017
Dubrovnik, Hrvatska