OC 68.5 - Plasma N-glycan signatures are associated with a first event of venous thromboembolism

Background: Coagulation factors play important roles in the pathophysiology of venous thromboembolism (VTE). The majority of them are glycoproteins, i.e., proteins containing glycans attached to amino acid side chains. Glycosylation affects the function of proteins in the plasma. Nonetheless, there is no study yet, to explore the role of glycosylation profile changes on VTE risk.

Aims: We aimed to elucidate the association between N-glycans in plasma and the risk of a first VTE in the Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis (MEGA) study, a large case-control study on factors for VTE.

Methods: As a pilot study, we randomly selected 509 VTE cases with a first, idiopathic VTE (i.e., without known environmental risk factors and not carrying FV Leiden or FII 20210A mutations) and 514 controls from the MEGA study. Using a robust mass spectrometry-based platform for analyzing the N-glycans of all plasma proteins in a single go, 100 N-glycans were measured in the samples and represented as relative abundance. Considering the characteristic of compositional data, centered log-ratio transformation was applied to the data before the analysis. The association between each N-glycan and the risk of a first VTE was analyzed using logistic regression, adjusting for age and sex. We used false discovery rate corrected q-value < 0.05 as the study-wise significance.

Results: In total 502 VTE cases (72% men, mean (SD) age of 54 years (12)) and 482 controls (62% men, mean (SD) age of 50 years (12)) passed quality control and were included in the analysis. Out of 100 measured N-glycans, 63 were significantly associated with VTE risk (Figure 1).

Conclusion(s): We demonstrated the relevance of plasma N-glycan signatures in the risk of VTE. Further refined analysis is planned to disentangle the biological mechanism.