Proteomic analysis reveals that apolipoprotein A1 levels are decreased in patients with Budd-Chiari syndrome

Background & Aims: Budd-Chiari syndrome (BCS) is a rare vascular liver disorder caused by thrombosis of the hepatic veins. In some patients, no known thrombophilic factor can be identified. This study aimed to identify novel factors that might play a role in thrombosis in BCS-patients by using a proteomic approach. Methods: The abundance of plasma clot-bound proteins was compared between nine BCS-patients and nine controls by using two-dimensional difference gel electrophoresis. The protein with the most significant decrease in patients was identified by mass spectrometry. Plasma levels of this protein were measured and the results were validated in a large cohort of BCS-patients. Results: A total of 26 protein spots significantly differed (p <0.001). The spot that decreased with the highest statistical significance in patients was identified by mass spectrometry as apolipoprotein A1 (apo A1). The mean level of apo A1 in the plasma of these BCS-patients (0.74 g/L) was also significantly lower than in controls (1.45 g/L, p = 0.002). This finding was validated in a large cohort of 101 BCS-patients and 101 controls (0.97 g/L vs. 1.32 g/L, p <0.0001). There was no major correlation between plasma levels of apo A1 and various liver function tests. Conclusions: BCS-patients show decreased clot-bound protein abundance and plasma levels of apo A1. Decreased levels of apo A1 may play a role in the etiology of thrombosis in BCS-patients and possibly in other patients with venous thrombosis.

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