I.V. Maliarchuk, N.G. Gorovenko, А.О. Krykunov, A.R. Babochkina.The clinical significance of G1639A polymorphic variants of VKORC1 gene for individualized therapy with warfarin

The aim – to investigate the impact of VKORC1 polymorphism on dosage of warfarin and international normalized ratio (INR).
Material and methods. The study included 155 patients after heart valve replacement. Patients received warfarin treatment from initial dose of 5 mg daily. Subgroup A (n=35) included patients with INR values out of therapeutic range and subgroup B (n=120) – patients with INR values in the range 2.5–3.5. For determination of polymorphic variant G1639A of VKORC1 gene the method of PCR-RFLP has been used.
Results. The frequencies of 1639GG, 1639GA and 1639AA genotypes among the patients group were 37.42 %, 46.45 %, 16.13 %, respectively. The mean warfarin daily dose requirement was the lowest in patients with genotypes VKORC1 1639AA and 1639GA compared to patients with genotype 1639GG (Р<0.05). Patients with genotype VKORC1 1639АА had higher risk of over-anticoagulation (INR > 3.5) during warfarin therapy, compared to patients with wild-type genotype (Р<0.05). Conclusions. Genotypes 1639GA and 1639AA are frequent enough to provide background for personalized warfarin dosing.

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