Analysis of PROS1, EPCR and PROC Single Nucleotide Polymorphisms in Patients with Myeloproliferative Neoplasms

Abstract

Background and Objectives Patients with Philadelphia-negative (Ph-) myeloproliferative neoplasms: primary myelofibrosis (PMF), essential thrombocythemia (ET) and polycythemia vera (PV); often encounter thrombotic events and other disease complications. It was suggested that the genetic variants that are responsible for blood coagulation play causal role in the development of thrombosis. In this work, we evaluated the effect of single nucleotide polymorphisms (SNPs) in PROS1, EPCR, PROC genes and the risk of developing thrombosis as well as clinical characteristics in patients with myeloproliferative disorders. Material and Method In the present study, we performed the analysis for PROS1 g.66847T>C, EPCR c.4678G>C, EPCR c.6936A>G, PROC c.565C>T polymorphisms for patients with myeloproliferative neoplasms. The study included 88 patients who were diagnosed with ET, PV or PMF between 2000 and 2014 at the Department of Hematology of the Institute of Oncology, the Lithuanian University of Health Sciences, Kaunas, Lithuania. Medical information was collected such as the patient’s age, sex, history of arterial or venous thrombosis, mean platelet volume, platelet count. Venous blood samples were collected in vacutainers with EDTA as anticoagulant. Genomic DNA was extracted from peripheral blood leukocytes using a commercially available DNA extraction kit, according to the instructions provided by the manufacturer (Thermo Fisher Scientific Baltics, Vilnius, Lithuania). Genomic variants in all of the cases were detected by employing a polymerase chain reaction - restriction fragment length polymorphism (PCRRFLP) method. Results After genotyping 88 patients with Ph- myeloproliferative neoplasms, regression analysis revealed that the carriers of PROS1 66847 TC (p=0.007; OR 0.063; 95% CI 0.008 – 0.471), EPCR 4678 GC (p<0.001; OR 0.226; 95% CI 0.099 – 0.513), EPCR 6936 AG (p<0.001; OR 0.171; 95% CI 0.077 – 0.381) or [...].