Abstract
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.
Highlights
Primary myelofibrosis (PMF) is a myeloproliferative disorder mostly caused by gain-of-function driver mutations in Janus kinase-2 (JAK2), calreticulin (CALR), or myeloproliferative leukemia virus (MPL).[1]
Frequency of rs3025020 minor allele (T) was not significantly different in subjects with primary myelofibrosis (PMF) compared with normals; the T-allele was more frequent in PMF subjects with a calreticulin (CALR)-mutated genotype compared with normals (35 vs. 27%; OR 1⁄4 1.47 [95% CI, 1.09, 1.98] p 1⁄4 0.011), especially in subjects with a CALRtype 2/type 2-like mutation (43 vs. 27%; OR 1⁄4 2.01 [1.25, 3.24] p 1⁄4 0.004)
When refining the assessment of Vascular endothelial growth factor A (VEGFA) rs3025020 status for the risk of thrombosis, we showed an increase in risk for CC genotype with respect to CT/TT genotype, with Subhazard ratio (sHR) for CT/TT 0.37 (0.14, 0.95) p 1⁄4 0.039
Summary
Single nucleotide polymorphisms (SNPs) in vascular endothelial growth factor A (VEGFA) are associated with susceptibility to several diseases including cancer. 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 1⁄4 0.37 [0.15, 0.90] p 1⁄4 0.029) and longer interval from diagnosis to first thrombosis (HR 1⁄4 0.37 [0.14, 0.95] p 1⁄4 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. E514 VEGFA rs3025020 Polymorphism Villani et al
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: TH open : companion journal to thrombosis and haemostasis
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
