The Inflammation Biomarker GlycA Reflects Plasma N-Glycan Branching

Clin Chem. 2023 Jan 4;69(1):80-87. doi: 10.1093/clinchem/hvac160.

Abstract

Background: GlycA is a nuclear magnetic resonance (NMR) signal in plasma that correlates with inflammation and cardiovascular outcomes in large data sets. The signal is thought to originate from N-acetylglucosamine (GlcNAc) residues of branched plasma N-glycans, though direct experimental evidence is limited. Trace element concentrations affect plasma glycosylation patterns and may thereby also influence GlycA.

Methods: NMR GlycA signal was measured in plasma samples from 87 individuals and correlated with MALDI-MS N-glycomics and trace element analysis. We further evaluated the genetic association with GlycA at rs13107325, a single nucleotide polymorphism resulting in a missense variant within SLC39A8, a manganese transporter that influences N-glycan branching, both in our samples and existing genome-wide association studies data from 22 835 participants in the Women's Health Study (WHS).

Results: GlycA signal was correlated with both N-glycan branching (r2 ranging from 0.125-0.265; all P < 0.001) and copper concentration (r2 = 0.348, P < 0.0001). In addition, GlycA levels were associated with rs13107325 genotype in the WHS (β [standard error of the mean] = -4.66 [1.2674], P = 0.0002).

Conclusions: These results provide the first direct experimental evidence linking the GlycA NMR signal to N-glycan branching commonly associated with acute phase reactive proteins involved in inflammation.

MeSH terms

  • Acetylglucosamine / analogs & derivatives
  • Acetylglucosamine / chemistry
  • Acute-Phase Proteins / analysis
  • Acute-Phase Proteins / chemistry
  • Biomarkers / chemistry
  • Cation Transport Proteins / genetics
  • Female
  • Genome-Wide Association Study
  • Humans
  • Inflammation* / diagnosis
  • Polysaccharides / chemistry
  • Trace Elements

Substances

  • Acute-Phase Proteins
  • Biomarkers
  • Polysaccharides
  • Trace Elements
  • Acetylglucosamine
  • SLC39A8 protein, human
  • Cation Transport Proteins