4G/5G polymorphism and plasma levels of plasminogen activator inhibitor-1 in essential thrombocythemia patients with driver mutational status

TL;DR

This study explores how a genetic variation and PAI-1 levels affect thrombosis risk in essential thrombocythemia patients with different mutations.

Contribution

The study identifies a link between 4G4G polymorphism and PAI-1 levels in JAK2-mutated ET patients and increased thrombosis risk.

Findings

JAK2 V617F mutation positive ET patients have higher thrombosis incidence compared to CALR mutation positive patients.

4G4G polymorphism and elevated PAI-1 levels are associated with increased thrombosis risk in JAK2-mutated ET patients.

PAI-1 levels and 4G4G genotype may serve as predictive markers for thrombosis in specific ET subtypes.

Abstract

Essential thrombocythemia (ET) is a kind of myeloproliferative neoplasms. Thrombosis is one of the common symptoms, however, the incidence of thrombosis in ET with JAK2, CALR, MPL gene mutations varies greatly, and the underlying mechanism is unclear. The clinical data of 155 consecutive patients with ET were analyzed retrospectively. The plasminogen activator inhibitor-1 (PAI-1) 4G/5G polymorphism and plasma levels were measured by sequencing reaction universal kit and enzyme linked immunosorbent assay (ELISA), respectively. The mutational status in ET was detected by polymerase chain reaction (PCR). Thrombotic events were detected by Color Doppler Ultrasound, Computer Tomography (CT), Magnetic Resonance Imaging (MRI), angiography and D-dimer. Among 155 patients with ET, 21.3% (33/155) had thrombotic events, including 54.5% (18/33) of ischemic stroke, 36.4% (12/33) of ischemic heart disease and 9.1% (3/33) of venous thrombosis. Compared to the healthy control population, there was no significant difference between the occurrence of thrombotic events and the patient’s age, gender, and blood cell counts, except for platelet counts. The incidence of thrombotic events in JAK2 V617F mutation positive ET patients was significantly higher than that in CALR mutation positive and JAK2 V617F mutation negative ET patients (P < 0.05). The gene 4G4G polymorphism and plasma levels of PAI-1 in JAK2 V617F mutated ET patients were significantly higher than that in CALR mutated ET patients, respectively (P < 0.05). In patients with JAK2 V617F mutation positive ET, the incidence of thrombosis in 4G4G gene group and plasma levels of PAI-1 group were significantly higher than that in non 4G4G group, respectively (P < 0.05). The 4G4G gene polymorphism and high plasma levels of PAI-1 have potential value in predicting the risk factors for thrombosis in JAK2 V617F mutation positive ET compare to CALR mutation positive subjects.