Villani Laura, Rosti Vittorio, Massa Margherita, Campanelli Rita, Catarsi Paolo, Carolei Adriana, Abbà Carlotta, de Silvstri Annalisa, Gale Robert Peter, Barosi Giovanni
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.
Laboratory of Biochemistry, Biotechnology and Advanced Diagnostics, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo Foundation, Pavia, Italy.
TH Open. 2021 Nov 9;5(4):e513-e520. doi: 10.1055/s-0041-1739293. eCollection 2021 Oct.
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.
血管内皮生长因子A（VEGF-A）中的单核苷酸多态性（SNP）与包括癌症在内的多种疾病易感性相关。VEGF-A基因型与原发性骨髓纤维化（PMF）临床及实验室特征之间的相关性尚未得到研究。通过实时聚合酶链反应对844例PMF患者队列以及两个正常受试者队列（n = 247和n = 107）的VEGF-A基因型进行DNA分析。与正常受试者相比，PMF患者中VEGF-A次要等位基因（T）的频率无显著差异；然而，与正常受试者相比，钙网蛋白（CALR）突变基因型的PMF患者中T等位基因更为常见（35%对27%；OR = 1.47 [95%CI，1.09，1.98]，P = 0.011），尤其是在CALR 2型/2型样突变患者中（43%对27%；OR = 2.01 [1.25，3.24]，P = 0.004）。携带VEGF-A TT基因型的CALR突变体在CD34阳性血细胞上CXCR4表达较高，且在诊断时，携带CT/TT基因型的患者血小板浓度低于其他基因型。总体而言，携带VEGF-A CT/TT基因型的患者在典型部位深静脉血栓形成的累积发生率较低（1.6%对4.2%；OR = 0.37 [0.15，0.90]，P = 0.029），从诊断到首次血栓形成的间隔时间更长（HR = 0.37 [0.14，0.95]，P = 0.039）。与其他体细胞驱动突变相比，携带PMF和VEGF-A次要T等位基因的患者更有可能发生CALR突变，且在典型部位深静脉血栓形成的累积发生率和风险较低。
