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

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...

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Autores principales:	Laura Villani, Vittorio Rosti, Margherita Massa, Rita Campanelli, Paolo Catarsi, Adriana Carolei, Carlotta Abbà, Annalisa de Silvstri, Robert Peter Gale, Giovanni Barosi
Formato:	article
Lenguaje:	EN
Publicado:	Georg Thieme Verlag KG 2021
Materias:	primary myelofibrosis vegfa polymorphism rs3025020 deep vein thrombosis calr mutation Diseases of the circulatory (Cardiovascular) system RC666-701
Acceso en línea:	https://doaj.org/article/e906254e58584b989aaa9b12fede141e
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spelling	oai:doaj.org-article:e906254e58584b989aaa9b12fede141e2021-11-09T23:57:38ZVEGFA rs3025020 Polymorphism Contributes to CALR-Mutation Susceptibility and Is Associated with Low Risk of Deep Vein Thrombosis in Primary Myelofibrosis2512-946510.1055/s-0041-1739293https://doaj.org/article/e906254e58584b989aaa9b12fede141e2021-10-01T00:00:00Zhttp://www.thieme-connect.de/DOI/DOI?10.1055/s-0041-1739293https://doaj.org/toc/2512-9465Background 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.Laura VillaniVittorio RostiMargherita MassaRita CampanelliPaolo CatarsiAdriana CaroleiCarlotta AbbàAnnalisa de SilvstriRobert Peter GaleGiovanni BarosiGeorg Thieme Verlag KGarticleprimary myelofibrosis vegfa polymorphism rs3025020 deep vein thrombosis calr mutationDiseases of the circulatory (Cardiovascular) systemRC666-701ENTH Open, Vol 05, Iss 04, Pp e513-e520 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	primary myelofibrosis vegfa polymorphism rs3025020 deep vein thrombosis calr mutation Diseases of the circulatory (Cardiovascular) system RC666-701
spellingShingle	primary myelofibrosis vegfa polymorphism rs3025020 deep vein thrombosis calr mutation Diseases of the circulatory (Cardiovascular) system RC666-701 Laura Villani Vittorio Rosti Margherita Massa Rita Campanelli Paolo Catarsi Adriana Carolei Carlotta Abbà Annalisa de Silvstri Robert Peter Gale Giovanni Barosi VEGFA rs3025020 Polymorphism Contributes to CALR-Mutation Susceptibility and Is Associated with Low Risk of Deep Vein Thrombosis in Primary Myelofibrosis
description	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.
format	article
author	Laura Villani Vittorio Rosti Margherita Massa Rita Campanelli Paolo Catarsi Adriana Carolei Carlotta Abbà Annalisa de Silvstri Robert Peter Gale Giovanni Barosi
author_facet	Laura Villani Vittorio Rosti Margherita Massa Rita Campanelli Paolo Catarsi Adriana Carolei Carlotta Abbà Annalisa de Silvstri Robert Peter Gale Giovanni Barosi
author_sort	Laura Villani
title	VEGFA rs3025020 Polymorphism Contributes to CALR-Mutation Susceptibility and Is Associated with Low Risk of Deep Vein Thrombosis in Primary Myelofibrosis
title_short	VEGFA rs3025020 Polymorphism Contributes to CALR-Mutation Susceptibility and Is Associated with Low Risk of Deep Vein Thrombosis in Primary Myelofibrosis
title_full	VEGFA rs3025020 Polymorphism Contributes to CALR-Mutation Susceptibility and Is Associated with Low Risk of Deep Vein Thrombosis in Primary Myelofibrosis
title_fullStr	VEGFA rs3025020 Polymorphism Contributes to CALR-Mutation Susceptibility and Is Associated with Low Risk of Deep Vein Thrombosis in Primary Myelofibrosis
title_full_unstemmed	VEGFA rs3025020 Polymorphism Contributes to CALR-Mutation Susceptibility and Is Associated with Low Risk of Deep Vein Thrombosis in Primary Myelofibrosis
title_sort	vegfa rs3025020 polymorphism contributes to calr-mutation susceptibility and is associated with low risk of deep vein thrombosis in primary myelofibrosis
publisher	Georg Thieme Verlag KG
publishDate	2021
url	https://doaj.org/article/e906254e58584b989aaa9b12fede141e
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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

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