[The Effect of 4 2 Polymorphism on Initial Warfarin Dose in Patients with Heart Valve Replacement].

Objective: To study the effect of cytochrome P-4504F2 ( 4 2) 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 4 2 gene type of each patient, and analyzed the effect of 4 2 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 4 2 genotypes. However, warfarin dose was higher in 4 2 TT genotype than in 4 2 CC carriers ((3.37±0.68) mg vs. (2.94±0.74) mg, <0.05) in INR≥2 group; In patients with the same genotype, the initial dose of warfarin in the 4 2 CC ((4.02±0.58) mg vs. (2.94±0.74) mg) and 4 2 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 ( <0.05). Gender, age, body mass index (BMI), comorbidities (hypertension, diabetes mellitus, coronary heart disease, atrial fibrillation), cytopigment P-450 2C9 ( 2 9), 4 2 and vitamin K peroxide-reductase complex 1 ( 1) 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/m ) +1.102× 4 2 genotype (CC or CT values 1, TT values 2) +2.147× 1 (AA or AG values 1, GG values 2) +1.325×INR ( INR≥2 values 0, INR<2 values 1). The coefficient of determination ( ) of regression equation was 0.431 ( <0.05).

Conclusion: 4 2 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.