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.