More than half of all known proteins, and almost all membrane and extra-cellular proteins have oligosaccharide structures or glycans attached to them. Defects in glycosylation pathways are directly involved in at least 30 severe human diseases.A multiple center cross-sectional study (China, Croatia, and Scotland) was carried out to investigate the possible association between hypertension and IgG glycosylation. A hydrophilic interaction chromatography of fluorescently labeled glycans was used to analyze N-glycans attached to IgG in plasma samples from a total of 4757 individuals of Chinese Han, Croatian, and Scottish ethnicity.Five glycans (IgG with digalactosylated glycans) significantly differed in participants with prehypertension or hypertension compared to those with normal blood pressure, while additional 17 glycan traits were only significantly differed in participants with hypertension compared to those of normal blood pressure. These glycans were also significant correlated with systolic blood pressure (SBP) or diastolic blood pressure (DBP).The present study demonstrated for the 1st time an association between hypertension and IgG glycome composition. These findings suggest that the individual variation in N-glycosylation of IgG contributes to pathogenesis of hypertension, presumably via its effect on pro- and/or anti-inflammatory pathways.

Suboptimal health status (SHS) is a physical state between health and disease, characterized by the perception of health complaints, general weakness, chronic fatigue and low energy levels. SHS is proposed by the ancient concept of traditional Chinese medicine (TCM) from the perspective of preservative, predictive and personalized (precision) medicine. We previously created the suboptimal health status questionnaire 25 (SHSQ-25), a novel instrument to measure SHS, validated in various populations. SHSQ-25 thus affords a window of opportunity for early detection and intervention, contributing to the reduction of chronic disease burdens. To investigate the causative effect of SHS in non-communicable chronic diseases (NCD), we initiated the China suboptimal health cohort study (COACS), a longitudinal study starting from 2013. Phase I of the study involved a cross-sectional survey aimed at identifying the risk/protective factors associated with SHS; and Phase II: a longitudinal yearly follow-up study investigating how SHS contributes to the incidence and pattern of NCD. (1) Cross-sectional survey: in total, 4313 participants (53.8 % women) aged from 18 to 65 years were included in the cohort. The prevalence of SHS was 9.0 % using SHS score of 35 as threshold. Women showed a significantly higher prevalence of SHS (10.6 % in the female vs. 7.2 % in the male, P < 0.001). Risk factors for chronic diseases such as socioeconomic status, marital status, highest education completed, physical activity, salt intake, blood pressure and triglycerides differed significantly between subjects of SHS (SHS score ≥35) and those of ideal health (SHS score <35). (2) Follow up: the primary and secondary outcomes will be monitored from 2015 to 2024. The sex-specific difference in prevalence of SHS might partly explain the gender difference of incidence of certain chronic diseases. The COACS will enable a thorough characterization of SHS and establish a cohort that will be used for longitudinal analyses of the interaction between the genetic, lifestyle and environmental factors that contribute to the onset and etiology of targeted chronic diseases. The study together with the designed prospective cohort provides a chance to characterize and evaluate the effect of SHS systemically, and it thus generates an unprecedented opportunity for the early detection and prevention of chronic disease.

Glycosylation significantly affects protein structure and function and thus participates in multiple physiologic and pathologic processes. Studies demonstrated that immunoglobulin G (IgG) N-glycosylation associates with the risk factors of ischemic stroke (IS), such as aging, obesity, dyslipidemia, type 2 diabetes, and hypertension. The study aimed to investigate the association between IgG N-glycosylation and IS in a Chinese population. IgG glycome composition in patients with IS (n = 78) and cerebral arterial stenosis (CAS) (n = 75) and controls (n = 77) were analyzed by ultra-performance liquid chromatography. Eleven initial glycans and 10 derived glycans in IgG glycome representing galactosylation, sialylation, and bisecting GlcNAc significantly differed between IS patients and CAS and healthy controls after controlling for gender, age, obesity, diabetes, hypertension, and dyslipidemia. Logistic regression models incorporating IgG glycan traits were able to distinguish IS from CAS (area under receiver–operator characteristic curves (AUC), 0.802; 95% confidence interval (CI), 0.732–0.872) and controls (AUC, 0.740; 95% CI, 0.661–0.819). The canonical correlation analysis indicated that initial N-glycan structures are significantly correlated with inflammation markers (r = 0.566, p < 0.001). Our findings indicated that loss of galactose and sialic acid, as well as addition of bisecting GlcNAc, might involve in pro- or anti-inflammatory IgG functionality and further contribute to the pathogenesis of IS. IgG glycan profiles may be developed as clinical useful biomarkers for chronic disease in the future.

Alternative N-glycosylation has significant structural and functional consequences on immunoglobulin G (IgG) and can affect immune responses, acting as a switch between pro- and anti-inflammatory IgG functionality. Studies have demonstrated that IgG N-glycosylation is associated with ageing, body mass index, type 2 diabetes and hypertension. Herein, we have demonstrated patterns of IgG glycosylation that are associated with blood lipids in a cross-sectional study including 598 Han Chinese aged 20–68 years. The IgG glycome composition was analysed by ultra-performance liquid chromatography. Blood lipids were positively correlated with glycan peak GP6, whereas they were negatively correlated with GP18 (P < 0.05/57). The canonical correlation analysis indicated that initial N-glycan structures, including GP4, GP6, GP9-12, GP14, GP17, GP18 and GP23, were significantly correlated with blood lipids, including total cholesterol, total triglycerides (TG) and low-density lipoprotein (r = 0.390, P < 0.001). IgG glycans patterns were able to distinguish patients with dyslipidaemia from the controls, with an area under the curve of 0.692 (95% confidence interval 0.644–0.740). Our findings indicated that a possible association between blood lipids and the observed loss of galactose and sialic acid, as well as the addition of bisecting GlcNAcs, which might be related to the chronic inflammation accompanying with the development and procession of dyslipidaemia.