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

Single nucleotide polymorphisms (SNPs) in vascular endothelial growth factor A ( ) are associated with susceptibility to several diseases including cancer. Correlations between genotypes with clinical and laboratory features of primary myelofibrosis (PMF) are unstudied.  DNA was analyzed by real-time polymerase chain reaction for genotypes in a cohort of 844 subjects with PMF and in two cohorts of normal subjects (  = 247 and  = 107).  Frequency of 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 ( )-mutated genotype compared with normals (35 vs. 27%; OR = 1.47 [95% CI, 1.09, 1.98]  = 0.011), especially in subjects with a type 2/type 2-like mutation (43 vs. 27%; OR = 2.01 [1.25, 3.24]  = 0.004). mutants with the 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 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]  = 0.029) and longer interval from diagnosis to first thrombosis (HR = 0.37 [0.14, 0.95]  = 0.039).  Persons with PMF and the minor T-allele are more likely to have a mutation compared with other somatic driver mutations and lower cumulative incidence and hazard for deep vein thrombosis in typical sites.