Glycosylation Profile of Immunoglobulin G Is Cross-Sectionally Associated With Cardiovascular Disease Risk Score and Subclinical Atherosclerosis in Two Independent Cohorts

Circ Res. 2018 May 25;122(11):1555-1564. doi: 10.1161/CIRCRESAHA.117.312174. Epub 2018 Mar 13.


Rationale: One measure of protein glycosylation (GlycA) has been reported to predict higher cardiovascular risk by reflecting inflammatory pathways.

Objective: The main objective of this study is to assess the role of a comprehensive panel of IgG glycosylation traits on traditional risk factors for cardiovascular disease and on presence of subclinical atherosclerosis in addition to GlycA.

Methods and results: We measured 76 IgG glycosylation traits in 2970 women (age range, 40-79 years) from the TwinsUK cohort and correlated it to their estimated 10-year atherosclerotic cardiovascular disease risk score and their carotid and femoral plaque measured by ultrasound imaging. Eight IgG glycan traits are associated with the 10-year atherosclerotic cardiovascular disease risk score after adjusting for multiple tests and for individual risk factors-5 with increased risk and 3 with decreased risk. These glycans replicated in 967 women from ORCADES cohort (Orkney Complex Disease Study), and 6 of them were also associated in 845 men. A linear combination of IgG glycans and GlycA is also associated with presence of carotid (odds ratio, 1.55; 95% confidence interval, 1.25-1.93; P=7.5×10-5) and femoral (odds ratio, 1.32; 95% confidence interval, 1.06-1.64; P=0.01) plaque in a subset of women with atherosclerosis data after adjustment for traditional risk factors. One specific glycosylation trait, GP18-the percentage of FA2BG2S1 glycan in total IgG glycans, was negatively correlated with very-low-density lipoprotein and triglyceride levels in serum and with presence of carotid plaque (odds ratio, 0.60; 95% confidence interval, 0.50-0.71; P=5×10-4).

Conclusions: We find molecular pathways linking IgG to arterial lesion formation. Glycosylation traits are independently associated with subclinical atherosclerosis. One specific trait related to the sialylated N-glycan is negatively correlated with cardiovascular disease risk, very-low-density lipoprotein and triglyceride serum levels, and presence of carotid plaque.

Keywords: atherosclerosis; cardiovascular disease risk; glycosylation; immunoglobulin G; plaque, atherosclerotic.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Atherosclerosis / complications*
  • Atherosclerosis / diagnostic imaging
  • Atherosclerosis / metabolism
  • Cardiovascular Diseases / etiology*
  • Cardiovascular Diseases / metabolism
  • Carotid Artery Diseases / diagnostic imaging
  • Carotid Artery Diseases / metabolism
  • Cohort Studies
  • Confidence Intervals
  • Diseases in Twins / etiology*
  • Diseases in Twins / metabolism
  • Female
  • Femoral Artery / diagnostic imaging
  • Glycosylation
  • Humans
  • Immunoglobulin G / metabolism*
  • Male
  • Middle Aged
  • Odds Ratio
  • Plaque, Atherosclerotic / diagnostic imaging
  • Plaque, Atherosclerotic / etiology
  • Plaque, Atherosclerotic / metabolism
  • Polysaccharides / metabolism
  • Risk Assessment
  • Risk Factors
  • Ultrasonography


  • Immunoglobulin G
  • Polysaccharides