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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

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 unstud...

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Autores principales: Villani, Laura, Rosti, Vittorio, Massa, Margherita, Campanelli, Rita, Catarsi, Paolo, Carolei, Adriana, Abbà, Carlotta, de Silvstri, Annalisa, Gale, Robert Peter, Barosi, Giovanni
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Georg Thieme Verlag KG 2021
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8577885/
https://www.ncbi.nlm.nih.gov/pubmed/34778698
http://dx.doi.org/10.1055/s-0041-1739293
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author Villani, Laura
Rosti, Vittorio
Massa, Margherita
Campanelli, Rita
Catarsi, Paolo
Carolei, Adriana
Abbà, Carlotta
de Silvstri, Annalisa
Gale, Robert Peter
Barosi, Giovanni
author_facet Villani, Laura
Rosti, Vittorio
Massa, Margherita
Campanelli, Rita
Catarsi, Paolo
Carolei, Adriana
Abbà, Carlotta
de Silvstri, Annalisa
Gale, Robert Peter
Barosi, Giovanni
author_sort Villani, Laura
collection PubMed
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.
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spelling pubmed-85778852021-11-12 VEGFA rs3025020 Polymorphism Contributes to CALR -Mutation Susceptibility and Is Associated with Low Risk of Deep Vein Thrombosis in Primary Myelofibrosis Villani, Laura Rosti, Vittorio Massa, Margherita Campanelli, Rita Catarsi, Paolo Carolei, Adriana Abbà, Carlotta de Silvstri, Annalisa Gale, Robert Peter Barosi, Giovanni TH Open 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. Georg Thieme Verlag KG 2021-11-09 /pmc/articles/PMC8577885/ /pubmed/34778698 http://dx.doi.org/10.1055/s-0041-1739293 Text en The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ) https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Villani, Laura
Rosti, Vittorio
Massa, Margherita
Campanelli, Rita
Catarsi, Paolo
Carolei, Adriana
Abbà, Carlotta
de Silvstri, Annalisa
Gale, Robert Peter
Barosi, Giovanni
VEGFA rs3025020 Polymorphism Contributes to CALR -Mutation Susceptibility and Is Associated with Low Risk of Deep Vein Thrombosis in Primary Myelofibrosis
title 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_short 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
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8577885/
https://www.ncbi.nlm.nih.gov/pubmed/34778698
http://dx.doi.org/10.1055/s-0041-1739293
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