Genetic polymorphisms of hemostatic factors and thrombotic risk in non BCR-ABL myeloproliferative neoplasms: A pilot study

Abstract

The most important complications of Philadelphianegagive (non BCR-ABL) myeloproliferative neoplasms (MPNs) are vascular events. Our aim was to evaluate the effects of single nucleotide polymorphisms (SNPs), platelet glycoproteins (GPs) (Ia/IIa, Ibα, IIb/IIIa and VI), von Willebrand factor (vWF), coagulation factor VII (FVII), β-fibrinogen, and the risk of thrombosis in patients with non BCR-ABL MPNs at the Lithuanian University of Health Sciences. Kaunas, Lithuania. Genotyping was done for 108 patients. The TT genotype of the GP Ia/IIa c.807C>T polymorphism was more frequently found in the group of MPN patients with arterial thrombosis compared to MPN patients who were thrombosis-free [26.5 vs. 11.5%, p = 0.049; odds ratio (OR) 2.68; 95% confidence interval (95% CI) 1.01-7.38]. The CT genotype of the β-fibrinogen c.-148C>T polymorphism occurred more frequently in MPN patients with arterial, and total thrombosis compared to the wild or homozygous genotype (57.7 vs. 40.0 vs. 12.5%; p = 0.027), (64.7 vs. 44.4 vs. 25%; p = 0.032), respectively. The carrier state for the c.-323P10 variant of FVII SNP (summation of P10/10 and P0/10) was more frequent in MPN patients with thrombosis compared to the wild-type genotype carriers (71.4 vs. 43.4%; p = 0.049; OR 3.26; 95% CI 1.01-11.31). The coexistence of heterozygous β-fibrinogen c.-148C>T and FVII c.-323P0/10 SNP, increased the risk of arterial thrombosis (21.1 vs. 3.7%, p = 0.008; OR 6.93; 95% CI 1.38-34.80). The TT genotype of GP Ia/IIa c.807C>T, the CT genotype of β-fibrinogen c.-148C>T and FVII c.-323P0/10 SNP could be associated with risk of thrombosis in MPN patients.

Molecular Genetics of Thrombotic Myeloproliferative Neoplasms: Implications in Precision Oncology

“…However, HPA-1a/1b GPIIIa variant failed to show any thrombosis correlation between PV and ET patients [149]. Study on another GPIa/IIa c.807C > T polymorphism [150], MPN patients with arterial thrombosis exhibited a higher frequency of TT genotype (26.5 vs. 11.5%, p = 0.049; odds ratio 2.68). Genetic predisposition may be stacked up in patients with MPN when SNPs affecting DNA repair and apoptosis are present.…”

“…Another gene polymorphisms within the β-fibrinogen (FBG), the heterozygous CT genotype of FBG c.-148C > T polymorphism is crucially higher (p = 0.02) in MPN patients with thrombotic events (57.7%) than CC wild type (40.0%) or TT homozygous (12.5%), but not for −455G/A FBG polymorphism [149]. Moreover, the presence of polymorphism in clotting factor II (F2) or G20210A mutation of prothrombin and clotting factor V (F5) or Leiden mutation has no significant association with thrombosis in patients with PV and ET [150,152]. A different outcome was obtained from another study [153], which found no difference between F5 mutation and arterial thrombosis (p = 0.337), but a higher rate of detection of venous thrombosis before and at time of diagnosis and recurrence of venous thrombosis in patients with PV and ET (p = 0.03).…”

“…In addition, the possibility of developing arterial thrombosis increases when both heterozygous FBG c.-148C > T and F7 c.-323P0/10 SNP coexisted at the same time (p = 0.008). Hence, it was suggested that coexistence of different polymorphisms may contribute to the pathophysiology of thrombosis in MPN [150]. Another clotting factor, factor XII (F12), with −46C/T F12 polymorphism did not correlate with thrombotic complication in patients with PV and ET [149].…”

Genetic factors that may affect the risk of developing thrombosis in patients with myeloproliferative disorders

“…Myeloproliferative neoplasms (MPNs), by definition, are clonal hematologic diseases that occur by overproduction of active blood cells [1]. The group of Philadelphia-negative (Ph-, non BCR-ABL) myeloproliferative neoplasms, polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), are known for their different phenotypes but similar complications [2]. Primary myelofibrosis specifically is a clonal stem cell disorder that is characterized by chronic myeloproliferation, megakaryocytic hyperplasia and the presence of the myeloid series immature cells in the circulating blood [3].…”