Glycomics for type 2 diabetes biomarker discovery: Promise of immunoglobulin G subclass-specific fragment crystallizable N-glycosylation in the Uyghur population

Author Identifier

wei wang

https://orcid.org/0000-0002-1430-1360

Document Type

Journal Article

Publication Title

OMICS : A Journal of Integrative Biology

Publisher

Mary Ann Liebert

School

School of Medical and Health Sciences

RAS ID

30010

Funders

National Health and Medical Research Council (NHMRC).

Further funding information available at: https://doi.org/10.1089/omi.2019.0052

Grant Number

NHMRC Number : 1112767

Comments

Liu, J., Dolikun, M., Štambuk, J., Trbojević-Akmačić, I., Zhang, J., Zhang, J., ... Wang, W. (2019). Glycomics for type 2 diabetes biomarker discovery: Promise of immunoglobulin G subclass-specific fragment crystallizable N-glycosylation in the Uyghur population. OMICS: A Journal of Integrative Biology, 23(12), 640-648. Available here

Abstract

Aberrant immunoglobulin G (IgG) N-glycosylation offers new prospects to detect changes in cell metabolism and by extension, for biomarker discovery in type 2 diabetes mellitus (T2DM). However, past studies did not analyze the individual IgG subclasses in relation to T2DM pathophysiology. We report here original findings through a comparison of the IgG subclass-specific fragment crystallizable (Fc) glycan biosignatures in 115 T2DM patients with 122 healthy controls within the Uyghur population in China. IgG Fc glycosylation profiles were analyzed using nano-liquid chromatography-mass spectrometry to exclude changes attributed to fragment antigen binding N-glycosylation. After correction for clinical covariates, 27 directly measured and 4 derived glycan traits of the IgG subclass-specific N-glycopeptides were significantly associated with T2DM. Furthermore, we observed in T2DM a decrease in bisecting N-acetylglucosamine of IgG2 and agalactosylation of IgG4, and an increase in sialylation of IgG4 and digalactosylation of IgG2. Classification model based on IgG subclass-specific N-glycan traits was able to distinguish patients with T2DM from controls with an area under the receiver operating characteristic curve of 0.927 (95% confidence interval 0.894-0.960, p < 0.001). In conclusion, a robust association between the IgG subclass-specific Fc N-glycomes and T2DM was observed in the Uyghur population sample in China, suggesting a potential for the IgG Fc glycosylation as a biomarker candidate for type 2 diabetes. The integration of glycomics with other system science biomarkers might offer further hope for innovation in diagnosis and treatment of T2DM in the future. Finally, it is noteworthy that "Population Glycomics" is an emerging approach to biomarker discovery for common complex diseases.

DOI

10.1089/omi.2019.0052

Access Rights

free_to_read

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