Matrix Metalloproteinases Family Gene Polymorphisms Are Associated with Thrombosis Risk in Myeloproliferative Neoplasms

TL;DR

This study finds that certain genetic variations in the MMP-9 gene are linked to a higher risk of blood clots in patients with myeloproliferative neoplasms.

Contribution

The study identifies specific MMP-9 gene polymorphisms as potential predictive markers for thrombosis risk in MPN patients.

Findings

The MMP-9 rs3918242 CT genotype is associated with increased risk of arterial thrombosis in MPN patients.

The same genotype is linked to overall thrombotic events, suggesting a role in MPN-related prothrombotic phenotype.

Abstract

Myeloproliferative neoplasms (MPNs) are clonal hematopoietic disorders characterized by excessive proliferation of one or more myeloid lineages, frequently accompanied by an elevated risk of thrombotic events. Matrix metalloproteinases (MMPs), a family of zinc-dependent endopeptidases, are implicated in numerous inflammatory and vascular pathophysiological processes. In this study, we analyzed the association between selected MMP polymorphisms, rs1799750, rs243865, rs3025058, rs3918242, and rs17576, and thrombotic risk as well as clinical characteristics in patients with MPNs. Genotyping was performed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Among the polymorphisms analyzed, a statistically significant association was identified between the MMP-9 rs3918242 CT genotype and an increased risk of arterial thrombosis (OR = 4.206, CI 1.337–13.234, p = 0.014). Moreover, rs3918242 CT was associated with thrombotic events (both arterial and venous thrombosis combined), suggesting a potential contributory role in the prothrombotic phenotype observed in MPNs (OR = 3.200, CI 1.110–9.258, p = 0.031). These findings indicate that genetic variation in MMP-9, particularly rs3918242, may serve as a predictive marker for vascular complications in MPN patients. Further studies with larger cohorts are warranted to confirm these associations and to elucidate the molecular mechanisms underlying the contribution of MMP polymorphisms to thrombosis in MPNs.