Abstract
One measure of protein glycosylation (GlycA) has been reported to predict higher cardiovascular risk by reflecting inflammatory pathways. 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. 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). 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.
Highlights
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
A linear combination of IgG glycans and GlycA is associated with presence of carotid and femoral plaque in a subset of women with atherosclerosis data after adjustment for traditional risk factors
This identified 46 glycan traits significantly associated with the 10-year atherosclerotic cardiovascular disease (ASCVD) risk score; 25 glycan traits were positively associated with the 10-year ASCVD risk score, whereas 21 were negatively associated (Online Table I)
Summary
The TwinsUK data that support the findings of this study are publicly available on request on the department website To access the ORCADES data, please email jim.wilson @ed.ac.uk. Study subjects were individuals enrolled in the TwinsUK registry, a national register of adult twins.[23] In this study, we analyzed data from 2970 females, 40 to 79 years old and without CVD. They had glycomics data available and the 10-year ASCVD risk score. The study was approved by St. Thomas’ Hospital Research Ethics Committee, and all twins provided informed written consent
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