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

TY - JOUR

T1 - Glycosylation Profile of Immunoglobulin G Is Cross-Sectionally Associated with Cardiovascular Disease Risk Score and Subclinical Atherosclerosis in Two Independent Cohorts

AU - Menni, Cristina

AU - Gudelj, Ivan

AU - MacDonald-Dunlop, Erin

AU - Mangino, Massimo

AU - Zierer, Jonas

AU - Bešić, Erim

AU - Joshi, Peter

AU - Trbojević-Akmačić, Irena

AU - Chowienczyk, Phil J

AU - Spector, Timothy D

AU - Wilson, James F

AU - Lauc, Gordan

AU - Valdes, Ana M

PY - 2018/3/16

Y1 - 2018/3/16

N2 - Rationale: One measure of protein glycosylation (GlycA) has been reported to predict higher cardiovascular risk by reflecting inflammatory pathways. Objective: To assess the role of a comprehensive panel of immunoglobulin (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 (ASCVD) risk score and their carotid and femoral plaque measured by ultrasound imaging. Eight IgG glycan traits are associated with the 10-year ASCVD 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, six of them were also associated in 845 men. A linear combination of IgG glycans and GlycA is also associated with presence of carotid (OR[95%CI]=1.55 [1.25;1.93], P=7.5X10-5) and femoral (OR[95%CI]==1.32[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 was negatively correlated with VLDL and triglyceride levels in serum and with presence of carotid plaque (OR[95%CI] = 0.60[0.50;0.71], P = 5x10-4). 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 CVD risk, VLDL and triglyceride serum levels and presence of carotid plaque.

AB - Rationale: One measure of protein glycosylation (GlycA) has been reported to predict higher cardiovascular risk by reflecting inflammatory pathways. Objective: To assess the role of a comprehensive panel of immunoglobulin (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 (ASCVD) risk score and their carotid and femoral plaque measured by ultrasound imaging. Eight IgG glycan traits are associated with the 10-year ASCVD 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, six of them were also associated in 845 men. A linear combination of IgG glycans and GlycA is also associated with presence of carotid (OR[95%CI]=1.55 [1.25;1.93], P=7.5X10-5) and femoral (OR[95%CI]==1.32[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 was negatively correlated with VLDL and triglyceride levels in serum and with presence of carotid plaque (OR[95%CI] = 0.60[0.50;0.71], P = 5x10-4). 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 CVD risk, VLDL and triglyceride serum levels and presence of carotid plaque.

KW - Journal Article

U2 - 10.1161/CIRCRESAHA.117.312174

DO - 10.1161/CIRCRESAHA.117.312174

M3 - Article

C2 - 29535164

SN - 0009-7330

VL - 122

SP - 1555

EP - 1564

JO - Circulation Research

JF - Circulation Research

IS - 11

ER -