Clinical Relevance of VEGFA (rs3025039) +936 C>T Polymorphism in Primary Myelofibrosis: Susceptibility, Clinical Co-Variates, and Outcomes

We evaluated the association of VEGFA rs3025039 polymorphism with clinical co-variates and outcomes in 849 subjects with primary myelofibrosis (PMF) and 250 healthy controls. Minor T-allele frequency was higher in subjects with JAK2(V617F) compared with those without JAK2(V617F) (18% vs. 13%; p = 0.014). In subjects with JAK2(V617F), the TT genotype was associated at diagnosis with lower platelet concentrations (p = 0.033), higher plasma LDH concentration (p = 0.005), higher blood CD34-positive cells (p = 0.027), lower plasma cholesterol concentration (p = 0.046), and higher concentration of high-sensitivity C-reactive protein (p = 0.018). These associations were not found in subjects with PMF without JAK2(V617F). In subjects with the TT genotype, risk of death was higher compared with subjects with CC/CT genotypes (HR = 2.12 [1.03, 4.35], p = 0.041). Finally, the TT genotype was associated with higher frequency of deep vein thrombosis in typical sites (12.5% vs. 2.5%; OR = 5.46 [1.51, 19.7], p = 0.009). In conclusion, in subjects with PMF, the VEGFA rs3025039 CT or TT genotypes are more common in those with JAK2(V617F) than in those without JAK2(V67F) mutation and are associated with disease severity, poor prognosis, and risk of deep vein thrombosis.