Naslov
MGAT3 gene promoter methylation correlates with IgG glycosylation in inflammatory bowel disease (IBD)

Autori
Vojta, Aleksandar ; Markulin, Dora ; Klasić, Marija ; Trbojević-Akmačić, Irena ; Lauc, Gordan ; Zoldoš, Vlatka

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
12th Jenner Glycobiology and Medicine Symposium, Translational Glycobiology, From Bench to Bedside: PROGRAMME BOOK / BOOK OF ABSTRACTS / - , 2017, 114-115

Skup
12th Jenner Glycobiology and Medicine Symposium, Translational Glycobiology, From Bench to Bedside

Mjesto i datum
Dubrovnik, Hrvatska, 06.05.2017. - 09.05.2017

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
IBD, MGAT3 ; correlation ; CpG methylation ; glycosylation

Sažetak
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.

Izvorni jezik
Engleski

Znanstvena područja
Biologija

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