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CC BY 4.0 · TH Open 2021; 05(04): e513-e520
DOI: 10.1055/s-0041-1739293
Original Article

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

Laura Villani
1   Center for the Study of Myelofibrosis, Laboratory of Biochemistry, Biotechnology and Advanced Diagnostics, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico S. Matteo Foundation, Pavia, Italy
,
Vittorio Rosti
1   Center for the Study of Myelofibrosis, Laboratory of Biochemistry, Biotechnology and Advanced Diagnostics, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico S. Matteo Foundation, Pavia, Italy
,
Margherita Massa 
2   Laboratory of Biochemistry, Biotechnology and Advanced Diagnostics, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo Foundation, Pavia, Italy
,
Rita Campanelli 
1   Center for the Study of Myelofibrosis, Laboratory of Biochemistry, Biotechnology and Advanced Diagnostics, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico S. Matteo Foundation, Pavia, Italy
,
Paolo Catarsi
1   Center for the Study of Myelofibrosis, Laboratory of Biochemistry, Biotechnology and Advanced Diagnostics, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico S. Matteo Foundation, Pavia, Italy
,
Adriana Carolei
1   Center for the Study of Myelofibrosis, Laboratory of Biochemistry, Biotechnology and Advanced Diagnostics, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico S. Matteo Foundation, Pavia, Italy
,
Carlotta Abbà
1   Center for the Study of Myelofibrosis, Laboratory of Biochemistry, Biotechnology and Advanced Diagnostics, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico S. Matteo Foundation, Pavia, Italy
,
Annalisa de Silvstri
3   Biometry & Clinical Epidemiology, Scientific Direction, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo Foundation, Pavia, Italy
,
Robert Peter Gale
4   Department of Immunology and Inflammation, Centre for Haematology Research, Imperial College London, London SW7 2BU, United Kingdom
,
Giovanni Barosi 
1   Center for the Study of Myelofibrosis, Laboratory of Biochemistry, Biotechnology and Advanced Diagnostics, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico S. Matteo Foundation, Pavia, Italy
› Author Affiliations Funding The study is supported by AIRC 5 × 1000 call “Metastatic disease: the key unmet need in oncology” to MYNERVA project, #21267 (MYeloid Research Venture AIRC) and Ricerca Corrente IRCCS Policlinico San Matteo Foundation, Pavia, Italy, project number 874, code number 08054517, received by Vittorio Rosti (www.sanmatteo.org).
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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.

Keywords

primary myelofibrosis - VEGFA polymorphism - rs3025020 - deep vein thrombosis - CALR mutation

Informed Consent

Subjects gave written informed consent approved by the IRCCS Policlinico S. Matteo Foundation Institutional Ethics Committee to be included in the database. The Ethics Committee of the Hospital approved a separate written informed consent for subjects to donate blood and bone marrow samples for molecular research on their disease.


Supplementary Material



Publication History

Received: 15 April 2021

Accepted: 15 July 2021

Article published online:
09 November 2021

© 2021. 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/)

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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