A Case-control Study in an Orcadian Population Investigating the Relationship between Human Plasma N-glycans and Metabolic Syndrome

Abstract

Background: Alterations in glycosylation patterns have long been known to reflect changes in cell metabolism. In this study, we investigated the relationship between human N-glycan profiles and metabolic syndrome. Method:Between 2005 and 2011, 2,155 individuals from the Orkney Islands (UK) were recruited and biological material, alongside phenotypic measures were collected. Individual N-glycan profiles were measured in plasma using weak anion exchange high performance liquid chromatography and calibrated hydrophilic interaction liquid chromatography. Pre-specified criteria were used to identify 564 cases with metabolic syndrome and 1475 controls. We applied logistic regression to test for association between this binary outcome against measured plasma N-glycans. We also assessed the correlation between N-glycan traits and individual components of metabolic syndrome and compared this to results found in similar analyses based in Chinese and Croatian populations.Results: 21 N-glycan traits were found to be associated with either an increased or a decreased likelihood of participants having metabolic syndrome, including monosialylated plasma N-glycans (OR of 1.49 (95%CI 1.33, 1.67), q=1.26E-12) and core fucosylated plasma N-glycans (OR of 0.81(95% CI 0.72-0.90), q=7.75E-4). Notably, consistent results in both sections of this analysis demonstrated the protective association of higher levels of core fucosylated N-glycans. Conclusion:Our results demonstrate that metabolic syndrome is associated with an alteration in plasma N-glycosylation patterns. The metabolic role of core fucosylated N-glycans is of particular interest for future study.

N‐glycome signatures in human plasma: associations with physiology and major diseases

“…'s report may explain the contradictory findings. In contrast, in various large cohort studies using higher‐resolution techniques a reduced fucosylation of diantennary structures in T2D and metabolic syndrome was found, notably, in Caucasians as well as Chinese and Ghanaian populations, even after adjustment for possible confounders including age, sex, and BMI . Consistent results were reported for IgG fucosylation in the same, large T2D case–control cohort as presented here .…”

Polybrominated Diphenyl Ethers and Gut Microbiome Modulate Metabolic Syndrome–Related Aqueous Metabolites in Mice

“…Epidemiologic studies have found that patients diagnosed with metabolic syndrome have an altered N-glycan profile, with some components, including those with seven and eight mannose residues, being positively associated with signs of metabolic syndrome and some inversely (Lu et al, 2011;McLachlan et al, 2016). In this study, BDE-99 reduced Alg12 expression and the relative abundance of mannose in CV but not GF mice, suggesting that a PBDE microbial metabolite could also contribute to these changes.…”

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

“…In addition, total plasma N-glycans have been shown to be associated with risk factors of metabolic syndrome (Lu et al, 2011;McLachlan et al, 2016). The inflammatory role of IgG N-glycans, together with their association with the cardiometabolic risk factors, such as aging , central obesity (Russell et al, 2018), dyslipidemia (Liu et al, 2018a), and hyperglycemia (Ge et al, 2018), leads to the hypothesis of this study that the changes to IgG N-glycan profiles are involved in the pathogenesis of cardiometabolic disease by regulating the inflammatory response.…”