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

Autori
Menni, Cristina ; Gudelj, Ivan ; Macdonald- Dunlop, Erin ; Mangino, Massimo ; Zierer, Jonas ; Bešić, Erim ; Joshi, Peter K. ; Trbojević- Akmačić, Irena ; Chowienczyk, Phil J. ; Spector, Tim D. ; Wilson, James F. ; Lauc, Gordan ; Valdes, Ana M.

Izvornik
Circulation Research (0009-7330) 122 (2018), 11; 1555-1564

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
atherosclerosis ; cardiovascular disease risk ; glycosylation ; immunoglobulin G ; plaque, atherosclerotic

Sažetak
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.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Interdisciplinarne prirodne znanosti, Kliničke medicinske znanosti

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