Next-Generation (Glycomic) Biomarkers for Cardiometabolic Health: A Community-Based Study of Immunoglobulin G N-Glycans in a Chinese Han Population

Abstract

Cardiovascular disease is a common complex trait that calls for next-generation biomarkers for precision diagnostics and therapeutics. The most common type of post-translational protein modification involves glycosylation. Glycans participate in key intercellular and intracellular functions, such as protein quality control, cell adhesion, cell-cell recognition, signal transduction, cell proliferation, and cell differentiation. In this context, immunoglobulin G (IgG) N-glycans affect the anti-inflammatory and proinflammatory responses of IgG, and are associated with cardiometabolic risk factors such as aging, central obesity, dyslipidemia, and hyperglycemia. Yet, the role of such glycomic biomarkers requires evaluation in diverse world populations. We report here original observations on association of IgG N-glycan biosignatures with 15 cardiometabolic risk factors in a community-based cross-sectional study conducted in 701 Chinese Han participants. After controlling for age and sex, we found that the 16, 21, and 18 IgG N-glycan traits were significantly different in participants with and without metabolic syndrome, hypertriglyceridemic waist phenotype, or abdominal obesity, respectively. The canonical correlation analysis showed that IgG N-glycan profiles were significantly associated with cardiometabolic risk factors (r = 0.469, p < 0.001). Classification models based on IgG N-glycan traits were able to differentiate participants with (1) metabolic syndrome, (2) hypertriglyceridemic waist phenotype, or (3) abdominal obesity from controls, with an area under receiver operating characteristic curves (AUC) of 0.632 (95% confidence interval [CI], 0.574-0.691, p < 0.001), 0.659 (95% CI, 0.587-0.730, p < 0.001), and 0.610 (95% CI, 0.565-0.656, p < 0.001), respectively. These new data suggest that IgG N-glycans may play an important role in cardiometabolic disease pathogenesis by regulating the proinflammatory or anti-inflammatory responses of IgG. Looking into the future, IgG N-glycan biosignatures warrant further research in other world population samples with a view to applications in clinical cardiology and public health practice.

Glycosylation Biomarkers Associated with Age-Related Diseases and Current Methods for Glycan Analysis

“…Metabolic syndrome is associated with an increased risk for CVD [ 102 ], which results in 40% of all deaths and ranks as the leading cause in population aged 65 or older [ 103 ]. As well as metabolic syndrome, other conditions such as insulin resistance, MetS and prediabetes can lead to a set of metabolic abnormalities (cardiometabolic disease) which can eventually lead to CVD [ 21 ]. Several risk factors such as abdominal obesity, dyslipidemia, hyperglycemia and hypertension are related to cardiometabolic disease [ 104 ].…”

“…Consequently, the combination of different techniques is often necessary to determine the structure of a glycan, either alone or in association with a protein. Amongst the available techniques, electrophoresis [ 19 , 20 , 21 , 22 ], liquid chromatography coupled to mass spectrometry (LC-MS) [ 7 , 23 , 24 , 25 , 26 ] and nuclear magnetic resonance (NMR) [ 27 , 28 ] are the most frequently used. Differently from n -glycans, the determination of O-glycans has advanced slower because these have less, or none, defined sequence patterns and arrangements [ 29 , 30 ] limiting the research studies focused on them.…”

Variation of IgG N‐linked glycosylation profile in diabetic retinopathy

“…Both genetic and environmental factors affect the incidence and development of diabetes and its complications, and the glycosylation of IgG proteins is one of the most common post-translational modifications which is involved in almost all physiological processes of the body, such as signal pathways, cellular immunity, and the mutual recognition of proteins [22]. The variation of IgG glycosylation profiles, reflecting both the genetic and environmental characteristics [23], are reported to be associated with various diseases, especially the autoimmune diseases, and chronic metabolic and inflammatory diseases [24][25][26]. In fact, both the glycometabolism disorder and impaired immunologic function involve in the pathophysiological process of diabetes and DR.…”

“…26 Variations in IgG glycosylation profiles, reflecting both genetic and environmental characteristics, 27 are reported to be associated with various diseases, especially autoimmune diseases and chronic metabolic and inflammatory diseases. [28][29][30] In fact, both glycometabolism disorders and impaired immunologic function are involved in the pathophysiological process of diabetes and DR. In this study, we found that GP15, GP20, and IGP54 were negatively associated with the onset of DR, while IGP32 showed a positive association.…”

Knowledge Domain and Emerging Trends of IgG Glycosylation: A Bibliometric Study Based on CiteSpace

“…People's interest in the research of immunoglobulin G (Ig G) glycosylation has increased dramatically, and many magazines have published a large number of articles on IgG glycosylation. Many studies have shown that changes in Ig G glycosylation level and sugar chain structure are often accompanied by the occurrence and development of various chronic disease [6][7][8] ,Because Ig G glycosylation is highly heterogeneous and can be regarded as a disease phenotype, it may be used as a dynamic disease biomarker from the perspective of predictive, preventive and personalized medicine Thing [9][10][11][12][13][14] . With the rapid increase in the number of articles published, it becomes very di cult to identify new developments and new trends in IgG glycosylation research.…”