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.