Polymorphisms of CYP2C9 and VKORC1 genes and their association with calcification of heart valves in Chuvash patients with chronic rheumatic heart disease

Relevance. Patients with chronic rheumatic heart disease (CRHD) often require warfarin, individual sensitivity to which is determined by polymorphisms of the CYP2C9 and VKORC1 genes. Warfarin use is associated with arterial calcification, which is explained by inhibition of the matrix protein MGP. This may be significant in CRHD, a characteristic feature of which is calcification of the heart valves. Objective. To study the polymorphisms of CYP2C9 (C430T and A1075C), VKORC1 (−1639G>A), and their association with calcification of the heart valves in Chuvash patients with CRHD receiving warfarin. Methods. The study included patients meeting the following criteria: 18–80 years old, confirmed CRHD, warfarin therapy, self-identification as an ethnicChuvash. Calcification of the valves was confirmed by echocardiography. Genotyping was performed by PCR. Results. The frequency of the A allele of the VKORC1 gene (−1639G>A) was 48.60 %, the T allele (CYP2C9*2) — 10.15%, and the C allele (CYP2C9*3) — 4.05 %. Calcification of the heart valves was detected in 75.7 % of the examined patients: the aortic (50 %) and mitral (45.9 %) valves were most often affected, while the tricuspid valve was involved less often (4.1 %). Statistical analysis demonstrated a significant association between homozygous carriage of the VKORC1 (−1639G>A) allele A and the development of aortic valve calcification (p = 0.023), while the difference between the AA and GA groups also reached statistical significance (p = 0.021). Conclusion. Identification of VKORC1 genetic variants, as well as the association of carriage of the A allele in homozygous form with valve calcification in patients with CRHD receiving warfarin therapy, can help in personalizing anticoagulant therapy, taking into account both the risks of hypocoagulation and the possible progression of heart valve calcification.