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OMICS. 2019 Dec;23(12):631-639. doi: 10.1089/omi.2019.0075. Epub 2019 Sep 17.

Type 2 Diabetes Mellitus is Associated with the Immunoglobulin G N-Glycome through Putative Proinflammatory Mechanisms in an Australian Population.

Li X1, Wang H1,2, Russell A1,3, Cao W2, Wang X1, Ge S1,4, Zheng Y1, Guo Z1, Hou H5, Song M1,2, Yu X1,6, Wang Y2, Hunter M3,7, Roberts P1, Lauc G8,9, Wang W1,5,10.

Author information

1
School of Medical and Health Sciences, Edith Cowan University, Joondalup, Australia.
2
Beijing Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing, China.
3
School of Population and Global Health, University of Western Australia, Crawley, Australia.
4
Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.
5
School of Public Health, Shandong First Medical University (Shandong Academy of Medical Sciences), Taian, China.
6
Tiantan Hospital, Capital Medical University, Beijing, China.
7
Busselton Health Study Centre, Busselton Population Medical Research Institute, Busselton, Australia.
8
Genos Glycoscience Research Laboratory, BIOCentar, Zagreb, Croatia.
9
Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia.
10
The First Affiliated Hospital, Shantou University Medical College, Shantou, China.

Abstract

Type 2 diabetes mellitus (T2DM) is a common complex trait arising from interactions among multiple environmental, genomic, and postgenomic factors. We report here the first attempt to investigate the association between immunoglobulin G (IgG) N-glycan patterns, T2DM, and their clinical risk factors in an Australian population. N-glycosylation of proteins is one of the most frequently observed co- and post-translational modifications, reflecting, importantly, the real-time status of the interplay between the genomic and postgenomic factors. In a community-based case-control study, 849 participants (217 cases and 632 controls) were recruited from an urban community in Busselton, Western Australia. We applied the ultraperformance liquid chromatography method to analyze the composition of IgG N-glycans. We then conducted Spearman's correlation analyses to explore the association between glycan biomarker candidates and clinical risk factors. We performed area under the curve (AUC) analysis of the receiver operating characteristic curves by fivefold cross-validation for clinical risk factors, IgG glycans, and their combination. Two directly measured and four derived glycan peaks were significantly associated with T2DM, after correction for extensive clinical confounders and false discovery rate, thus suggesting that IgG N-glycan traits are highly correlated with T2DM clinical risk factors. Moreover, adding the IgG glycan profiles to fasting blood glucose in the logistic regression model increased the AUC from 0.799 to 0.859. The AUC for IgG glycans alone was 0.623 with a 95% confidence interval 0.580-0.666. In addition, our study provided new evidence of diversity in T2DM complex trait by IgG N-glycan stratification. Six IgG glycan traits were firmly associated with T2DM, which reflects an increased proinflammatory and biological aging status. In summary, our study reports novel associations between the IgG N-glycome and T2DM in an Australian population and the putative role of proinflammatory mechanisms. Furthermore, IgG N-glycomic alterations offer future prospects as inflammatory biomarker candidates for T2DM diagnosis, and monitoring of T2DM progression to cardiovascular disease or renal failure.

KEYWORDS:

Australian population; IgG; biomarkers; glycomics; inflammation; type 2 diabetes mellitus

PMID:
31526239
DOI:
10.1089/omi.2019.0075

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