The Effect of CYP4F2 Polymorphism on Initial Warfarin Dose in Patients with Heart Valve Replacement

  Objective  To study the effect of cytochrome P-4504F2 (CYP4F2) gene polymorphism on the initial dose of warfarin in patients after mechanical heart valve replacement.

  Methods  We collected 350 patients receiving warfarin after mechanical heart valve replacement from January 2013 to December 2015 in our hospital. According to the international standardized ratio (INR) ≥2 at the initial stage after surgery, the patients were divided into two groups: INR≥2 group and INR<2 group. We selected the blood samples of all the 350 patients with testing the CYP4F2 gene type of each patient, and analyzed the effect of CYP4F2 gene polymorphism on the initial dose of warfarin after mechanical heart valve replacement (the average daily dose during hospitalization of patients 5-10 days after mechanical heart valve replacement).

  Results  There was no statistical significance in the initial dose of warfarin among patients with different CYP4F2 genotypes. However, warfarin dose was higher in CYP4F2 TT genotype than in CYP4F2 CC carriers ((3.37±0.68) mg vs. (2.94±0.74) mg, P<0.05) in INR≥2 group; In patients with the same genotype, the initial dose of warfarin in the CYP4F2 CC ((4.02±0.58) mg vs. (2.94±0.74) mg) and CYP4F2 CT genotypes ((4.15±0.88) mg vs. (3.18±0.82) mg) of INR<2 group was higher than that in INR≥2 group (P<0.05). Gender, age, body mass index (BMI), comorbidities (hypertension, diabetes mellitus, coronary heart disease, atrial fibrillation), cytopigment P-450 2C9 (CYP2C9), CYP4F2 and vitamin K peroxide-reductase complex 1 (VKORC1) gene polymorphism and INR compliance were included in multiple linear regression analysis. The regression equation was as follows: warfarin initial dose (mg) =−8.634+0.352×BMI (kg/m²) +1.102×CYP4F2 genotype (CC or CT values 1, TT values 2) +2.147×VKORC1 (AA or AG values 1, GG values 2) +1.325×INR ( INR≥2 values 0, INR<2 values 1). The coefficient of determination (R²) of regression equation was 0.431 (P<0.05).

  Conclusion   CYP4F2 gene polymorphism may affect the initial dose of warfarin in patients after heart valve replacement, and this effect is also affected by body characteristics and other factors.