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Background   Single nucleotide polymorphisms (SNPs) in vascular endothelial growth factor A (  VEGFA  ) are associated with susceptibility to several diseases including cancer. Correlations between  VEGFA rs3025020  genotypes with clinical and laboratory features of primary myelofibrosis (PMF) are unstudied.    Methods   DNA was analyzed by real-time polymerase chain reaction for  VEGFA rs3025020  genotypes in a cohort of 844 subjects with PMF and in two cohorts of normal subjects (  N   = 247 and  N   = 107).    Results   Frequency of  rs3025020  minor allele (T) was not significantly different in subjects with PMF compared with normals; however, the T-allele was more frequent in PMF subjects with a calreticulin (  CALR  )-mutated genotype compared with normals (35 vs. 27%; OR = 1.47 [95% CI, 1.09, 1.98]  p   = 0.011), especially in subjects with a  CALR-  type 2/type 2-like mutation (43 vs. 27%; OR = 2.01 [1.25, 3.24]  p   = 0.004).  CALR  mutants with the  rs3025020  TT genotype had higher CXCR4 expression on CD34-positive blood cells, and those who carried CT/TT genotypes had lower platelet concentrations compared with other genotypes at diagnosis. Overall, subjects with the  rs3025020  CT/TT genotype had a lower cumulative incidence of deep vein thrombosis in typical sites (1.6 vs. 4.2%; OR = 0.37 [0.15, 0.90]  p   = 0.029) and longer interval from diagnosis to first thrombosis (HR = 0.37 [0.14, 0.95]  p   = 0.039).    Conclusion   Persons with PMF and the  VEGFA rs3025020  minor T-allele are more likely to have a  CALR  mutation compared with other somatic driver mutations and lower cumulative incidence and hazard for deep vein thrombosis in typical sites.

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VEGFA rs3025020 Polymorphism Contributes to CALR-Mutation Susceptibility and Is Associated with Low Risk of Deep Vein Thrombosis in Primary Myelofibrosis