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Promoter methylation of the MGAT3 and BACH2 genes correlates with the composition of the immunoglobulin G glycome in inflammatory bowel disease

Overview of attention for article published in Clinical Epigenetics, June 2018
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Title
Promoter methylation of the MGAT3 and BACH2 genes correlates with the composition of the immunoglobulin G glycome in inflammatory bowel disease
Published in
Clinical Epigenetics, June 2018
DOI 10.1186/s13148-018-0507-y
Pubmed ID
Authors

Marija Klasić, Dora Markulin, Aleksandar Vojta, Ivana Samaržija, Ivan Biruš, Paula Dobrinić, Nicholas T. Ventham, Irena Trbojević-Akmačić, Mirna Šimurina, Jerko Štambuk, Genadij Razdorov, Nicholas A. Kennedy, Jack Satsangi, Ana M. Dias, Salome Pinho, Vito Annese, Anna Latiano, Renata D’Inca, IBD consortium, Gordan Lauc, Vlatka Zoldoš

Abstract

Many genome- and epigenome-wide association studies (GWAS and EWAS) and studies of promoter methylation of candidate genes for inflammatory bowel disease (IBD) have demonstrated significant associations between genetic and epigenetic changes and IBD. Independent GWA studies have identified genetic variants in the BACH2, IL6ST, LAMB1, IKZF1, and MGAT3 loci to be associated with both IBD and immunoglobulin G (IgG) glycosylation. Using bisulfite pyrosequencing, we analyzed CpG methylation in promoter regions of these five genes from peripheral blood of several hundred IBD patients and healthy controls (HCs) from two independent cohorts, respectively. We found significant differences in the methylation levels in the MGAT3 and BACH2 genes between both Crohn's disease and ulcerative colitis when compared to HC. The same pattern of methylation changes was identified for both genes in CD19+ B cells isolated from the whole blood of a subset of the IBD patients. A correlation analysis was performed between the MGAT3 and BACH2 promoter methylation and individual IgG glycans, measured in the same individuals of the two large cohorts. MGAT3 promoter methylation correlated significantly with galactosylation, sialylation, and bisecting GlcNAc on IgG of the same patients, suggesting that activity of the GnT-III enzyme, encoded by this gene, might be altered in IBD. The correlations between the BACH2 promoter methylation and IgG glycans were less obvious, since BACH2 is not a glycosyltransferase and therefore may affect IgG glycosylation only indirectly. Our results suggest that epigenetic deregulation of key glycosylation genes might lead to an increase in pro-inflammatory properties of IgG in IBD through a decrease in galactosylation and sialylation and an increase of bisecting GlcNAc on digalactosylated glycan structures. Finally, we showed that CpG methylation in the promoter of the MGAT3 gene is altered in CD3+ T cells isolated from inflamed mucosa of patients with ulcerative colitis from a third smaller cohort, for which biopsies were available, suggesting a functional role of this glyco-gene in IBD pathogenesis.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 61 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 61 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 13 21%
Student > Master 7 11%
Student > Bachelor 5 8%
Researcher 5 8%
Professor 4 7%
Other 10 16%
Unknown 17 28%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 14 23%
Medicine and Dentistry 8 13%
Agricultural and Biological Sciences 6 10%
Pharmacology, Toxicology and Pharmaceutical Science 4 7%
Immunology and Microbiology 3 5%
Other 5 8%
Unknown 21 34%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 24 May 2019.
All research outputs
#15,009,334
of 23,088,369 outputs
Outputs from Clinical Epigenetics
#796
of 1,270 outputs
Outputs of similar age
#198,671
of 329,877 outputs
Outputs of similar age from Clinical Epigenetics
#23
of 29 outputs
Altmetric has tracked 23,088,369 research outputs across all sources so far. This one is in the 32nd percentile – i.e., 32% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,270 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.5. This one is in the 32nd percentile – i.e., 32% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 329,877 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 36th percentile – i.e., 36% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 29 others from the same source and published within six weeks on either side of this one. This one is in the 13th percentile – i.e., 13% of its contemporaries scored the same or lower than it.