VPB1313 - VKORC1 -1639AA Genotype as a Possible Risk Factor for Venous Thromboembolism in Elderly Patients with FV Leiden Mutation

Tuesday, July 12, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: Virtual

Presenting Author(s)

Sergey Kapustin, PhD

Leading Researcher
Russian Research Institute of Hematology and Transfusiology
Saint Petersburg, Saint Petersburg City, Russia

Co-Author(s)

Anna Chechulova, PhD

Researcher
Dzhanelidze Research Institute of Emergency Medicine
St. Petersburg, Saint Petersburg City, Russia
JD

Julia Drijun

Researcher
Russian Research Institute of Hematology and Transfusiology
Saint Petersburg, Saint Petersburg City, Russia
ZS

Zhanna Sidorova

Researcher
Russian Research Institute of Hematology and Transfusiology
Saint Petersburg, Saint Petersburg City, Russia
VB

Vyacheslav Burakov

Senior Researcher
Russian Research Institute of Hematology and Transfusiology
Saint Petersburg, Saint Petersburg City, Russia
VS

Vladimir Soroka

Head of the Department of Cardiovascular Surgery
Dzhanelidze Research Institute of Emergency Medicine
Saint Petersburg, Saint Petersburg City, Russia
VS

Vitaly Soldatenkov, PhD, MD

Head of the Surgery Department
Russian Scientific Research Institute of Hematology and Transfusiology
Saint-Petersburg, Saint Petersburg City, Russia
LP

Lyudmila Papayan

head of blood coagulation laboratory
Russian Research Institute of Haematology and Transfusiology
Saint Petersburg, Saint Petersburg City, Russia

Background: Vitamin K plays a crucial role in hemostasis by activating both procoagulant (FII, VII, IX, X) and anticoagulant (proteins C, S, Z) factors. Vitamin K-epoxide reductase 1 (VKORC1) G-1639A gene polymorphism affects enzyme activity and bioavailability of vitamin K. Little is known about the role of the VKORC1 G-1639A variation in venous thromboembolism (VTE) development, in particular, in patients with inherited thrombophilia.

Aims: To study the role of the VKORC1 G-1639A gene polymorphism in VTE development in patients from North-Western Russia.

Methods: We included 600 VTE patients (294 men and 306 women, mean age 43.6±15.3 years) originated from the North-Western region of Russia in the study. The control group (CG) consisted of 200 healthy individuals of the same origin. Genotyping for the VKORC1 G-1639A, FII G20210A and FV G1691A variations was performed by PCR-RFLP. Intergroup differences in genotype frequencies were assessed by Fisher’s exact test. The study was approved by the local ethical committee.

Results: Distribution of the VKORC1 G-1639A gene variants was similar in both VTE patients and controls. In the group of patients without FII and FV gene mutations, the frequency of the VKORC1 -1639AA genotype was almost equal to that in CG (17.1% vs. 16.5%, respectively). VKORC1 -1639AA genotype frequency in patients with the FV Leiden was 4-fold higher than in those having the FII G20210A mutation (19.6% vs. 4.4%, respectively; OR=5.2; p=0.021). Notably, among patients having FV Leiden variant, the VKORC1 -1639AA genotype frequency was much higher in the group with late-onset disease (after 45 years) compared to young VTE patients (31.6% vs. 11.9%; OR=3,4; p=0,02). Thus, in elderly VTE patients with FV Leiden, the VKORC1 -1639AA variant was almost 2-fold overrepresented when compared to CG (31.6% vs. 16.5%; OR=2,4; p=0,033).

Conclusion(s): We suggest that the VKORC1 -1639AA genotype could increase VTE risk in elderly patients with FV Leiden mutation.