Assessment of plasminogen activator inhibitor-1 4G/5G genetic polymorphism among Egyptian patients with Budd-Chiari syndrome

Abstract

Budd-Chiari Syndrome (BCS) is a rare but life-threatening disorder caused by obstruction of hepatic venous outflow, involving the hepatic veins and/or the supra-hepatic inferior vena cava. This leads to increased sinusoidal pressure, hepatic congestion, and may progress to fibrosis, cirrhosis, or fulminant hepatic failure. Fibrinolysis is tightly regulated by factors such as Plasminogen Activator Inhibitor-1 (PAI-1), which inhibits fibrinolytic activators and is linked to various thrombotic disorders. The 4G/5G polymorphism in the PAI-1 gene affects PAI-1 expression and has been associated with increased thrombosis risk. This study aimed to assess the presence of PAI-1 4G/5G polymorphism among adult BCS patients and correlate with other thrombophilia genetic aberrations among BCS patients; additionally, evaluate its relevance with other different thrombophilia risk factors. This study was a cross-sectional study conducted on 40 Budd Chiari syndrome patients who were attending tropical medicine department at Ain Shams University Hospitals during the period from November 2023 to April 2025. Informed written consent was obtained from all patients in the study. PAI-1 4G/5G gene polymorphism was detected by using of real time PCR technique. Our study revealed that 70% of our patients had multiple mutation but 30% had only one single mutation. PAI-1 Mutation was detected in 28 out of 40 patients (70%) (17.5% homozygous and 52.5% heterozygous mutation). A significant statistical difference was found between abdominal tenderness and PAI-1 groups (p value = 0.026). The PAI-1 groups also showed statistically significant difference as regards protein C and protein S (p value = 0.038 for both) among 28 patients with positive PAI-1, where 8/28 (28.6%) had PC deficiency and only one patient (3.6%) presented with concomitant PS deficiency. The PAI-1 4G/5G polymorphism can impair fibrinolysis, creating a prothrombotic state that contributes to Budd-Chiari Syndrome. Although the 4G/4G genotype carries a higher thrombosis risk, heterozygotes may also be affected. Identifying PAI-1 polymorphisms through genetic testing can aid in the diagnosis and management of BCS.