APPLICATION OF PHARMACOGENETICS TESTING IN PATIENTS WITH CARDIAC VALVE REPLACEMENT

DOI: https://doi.org/None

I.A. Goncharova (1,2), M.V. Golubenko (1,2), E.V.Gorbunova (2), R.R. Salahov (2), А.А. Markov (1), I.Y. Zhuravleva (2), О.А. Маkееvа (1,2), V.P. Puzyrev (1) 1 -Research Institute of Medical Genetics, Nab. Ushaiki, 10, Tomsk, Russian Federation, 634050; 2 -Research Institute for Complex Issues of Cardiovascular Diseases, Sosnovy boulevard, 6, Kemerovo, Russian Federation, 650002

Introduction. Pharmacogenetic testing allows of increasing efficacy of anticoagulation therapy, reducing time required for adjusting therapeutic dose, and considerably reducing number of complications. The aim of the study. To investigate the dependence of theraupetic warfarin dose on age, weight, height, smoking status, cordarone or statin taking, as well as on genetic polymorphisms CYP2C9 (rs1799853, rs1057910) and VKORC1 (rs9923231), in the sample of patients with cardiac valve replacement. Results. Among non-genetic factors, patient’s height and hepatic disease have the biggest influence on the individual warfarin dose. Among genetic factors, most contribution is made by rs9923231 in VKORC1 and genotype combination VKORC1/CYP2C9*3, for which the biggest difference in dose variability was observed between carriers of various genotypes: GG – 5,94 mg/day, AG – 4,25, АА – 3,61 for VKORC; GG/ AA – 6,15 mg/day, AA/AC – 2,50 for VKORC1/CYP2C9*3). Strong correlation (r=0,804) has been shown between the therapeutic warfarin dose and recommended dose which was calculated with the use of the special algorithm (http://www.warfarindosing.org). However, for 17,1% of patients the difference between recommended and actual therapeutic dose were more that 1 dosing unit (1,2–6,9 mg/day). This group was characterized by higher frequencies of ancestral genotype carriers: AA (100%) for CYP2C9*3 and GG (54,1%) for VCORC1. Conclusion. In case of warfarin prescription, the special attention should be paid to the carriers of genotypes АА (CYP2C9*3) and GG (VKORC1). Further studies are needed to uncover genetic variants associated with the individual sensitivity in these subjects
Keywords: 
genetic polymorphism CYP2C9, VKORC1, pharmacogenetics, warfarin sensitivity, patients with cardiac valve prostheses
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