title: Decanucleotide insertion polymorphism of F7 significantly influences the risk of thrombosis in patients with essential thrombocythemia.
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).
  
  
  METHODS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Hematology and Blood Coagulation, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria.
authors.forename: Veronika
authors.initials: V
authors.lastname: Buxhofer-Ausch
authors.forename: Damla
authors.initials: D
authors.lastname: Olcaydu
authors.forename: Bettina
authors.initials: B
authors.lastname: Gisslinger
authors.forename: Martin
authors.initials: M
authors.lastname: Schalling
authors.forename: Sophie
authors.initials: S
authors.lastname: Frantal
authors.forename: Jürgen
authors.initials: J
authors.lastname: Thiele
authors.forename: Leonhard
authors.initials: L
authors.lastname: Müllauer
authors.forename: Hans-Michael
authors.initials: HM
authors.lastname: Kvasnicka
authors.forename: Herbert
authors.initials: H
authors.lastname: Watzke
authors.forename: Robert
authors.initials: R
authors.lastname: Kralovics
authors.forename: Heinz
authors.initials: H
authors.lastname: Gisslinger
mesh_terms: D000328:Adult; D000368:Aged; D005167:Factor VII / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D016254:Mutagenesis, Insertional; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D009841:Oligonucleotides / Q000235:genetics; D011110:Polymorphism, Genetic; D055728:Primary Myelofibrosis / Q000150:complications / Q000235:genetics* / Q000473:pathology; D017452:Receptors, IgG / Q000235:genetics; D012307:Risk Factors; D013920:Thrombocythemia, Essential / Q000150:complications / Q000235:genetics* / Q000473:pathology; D013927:Thrombosis / Q000209:etiology / Q000235:genetics* / Q000473:pathology
chemical_list: C445323:FCGR2A protein, human; D009841:Oligonucleotides; D017452:Receptors, IgG; D005167:Factor VII; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III
keywords: essential thrombocythemia; myeloproliferative neoplasms; prefibrotic primary myelofibrosis; thrombophilic single nucleotide polymorphism; thrombosis risk