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

1Russian Research Institute of Hematology and Transfusiology, Saint Petersburg, Saint Petersburg City, Russia, 2Dzhanelidze Research Institute of Emergency Medicine, St. Petersburg, Saint Petersburg City, Russia, 3Dzhanelidze Research Institute of Emergency Medicine, Saint Petersburg, Saint Petersburg City, Russia, 4Russian Research Institute of Haematology and Transfusiology, Saint Petersburg, Saint Petersburg City, Russia

Abstract Number: VPB1313

Meeting: ISTH 2022 Congress

Theme: Venous Thromboembolism » Genetic Risk Factors of Thrombosis

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.

To cite this abstract in AMA style:

Kapustin S, Chechulova A, Drijun J, Sidorova Z, Burakov V, Soroka V, Soldatenkov V, Papayan L. VKORC1 -1639AA Genotype as a Possible Risk Factor for Venous Thromboembolism in Elderly Patients with FV Leiden Mutation [abstract]. https://abstracts.isth.org/abstract/vkorc1-1639aa-genotype-as-a-possible-risk-factor-for-venous-thromboembolism-in-elderly-patients-with-fv-leiden-mutation/. Accessed September 29, 2023.

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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/vkorc1-1639aa-genotype-as-a-possible-risk-factor-for-venous-thromboembolism-in-elderly-patients-with-fv-leiden-mutation/