Decanucleotide insertion polymorphism of F7 significantly influences the risk of thrombosis in patients with essential thrombocythemia

Eur J Haematol. 2014 Aug;93(2):103-11. doi: 10.1111/ejh.12307. Epub 2014 Apr 23.

Abstract

Objective: There is strong evidence that certain thrombophilic single nucleotide polymorphisms (SNPs) account for an increased risk of thrombosis. The additive impact of inherited thrombotic risk factors to a certain disease- immanent thrombotic risk is vastly unknown. Therefore, we aimed to investigate the influence of three novel, preselected SNPs on the risk of thrombosis in patients diagnosed with myeloproliferative neoplasm (MPN).

Method: In 167 patients with a diagnosis of essential thrombocythemia (ET) or prefibrotic primary myelofibrosis (PMF) thrombophilic SNPs in the genes of factor VII (F7), nitric oxide synthase 3 (NOS3) and FcɣRIIa (FCGR2A) were determined. Subsequently, the polymorphic variants were correlated with the incidence of major thrombosis after diagnosis.

Results: Decanucleotide insertion polymorphism of F7 emerged as an independent, significant risk factor for total thrombosis and arterial thrombosis in particular in the whole group of patients (P = 0.0007) as well as in the separate analysis of patients with ET (P = 0.0002).

Conclusion: Our results illustrate that the risk of thrombosis in MPN is significantly multiplied by inherited thrombophilic SNPs. This result points to the importance of a combined consideration of the inherited and the acquired hypercoagulable state in patients with MPN. Larger studies are needed to confirm and extend these important findings.

Keywords: essential thrombocythemia; myeloproliferative neoplasms; prefibrotic primary myelofibrosis; thrombophilic single nucleotide polymorphism; thrombosis risk.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Factor VII / genetics*
  • Female
  • Gene Expression
  • Humans
  • Male
  • Middle Aged
  • Mutagenesis, Insertional
  • Nitric Oxide Synthase Type III / genetics
  • Oligonucleotides / genetics
  • Polymorphism, Genetic*
  • Primary Myelofibrosis / complications
  • Primary Myelofibrosis / genetics*
  • Primary Myelofibrosis / pathology
  • Receptors, IgG / genetics
  • Risk Factors
  • Thrombocythemia, Essential / complications
  • Thrombocythemia, Essential / genetics*
  • Thrombocythemia, Essential / pathology
  • Thrombosis / etiology
  • Thrombosis / genetics*
  • Thrombosis / pathology

Substances

  • FCGR2A protein, human
  • Oligonucleotides
  • Receptors, IgG
  • Factor VII
  • NOS3 protein, human
  • Nitric Oxide Synthase Type III