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CYP4F2基因多态性对心脏机械瓣膜置换术后患者华法林初始剂量的影响

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

    摘要
  • 摘要:
      目的  研究细胞色素P-450 4F2（CYP4F2）基因多态性对心脏机械瓣膜置换术后患者华法林初始剂量的影响。
      方法  收集2013年1月−2015年12月期间于我院心脏外科接受心脏机械瓣膜置换术后需服用华法林的患者350例，华法林剂量术后初始阶段国际标准化比值（INR）≥2的患者称为达标组，INR<2的患者称为非达标组。留取血样标本检测每位患者的CYP4F2基因型，分析CYP4F2基因多态性对心脏机械瓣膜置换患者术后华法林初始剂量（心脏机械瓣膜术后5～10 d患者住院期间的平均每日剂量）的影响。
      结果  本研究发现在所有患者人群中，不同CYP4F2基因型患者间华法林的初始剂量差异无统计学意义；但在INR达标组的患者中，CYP4F2 TT基因型患者的华法林初始剂量高于CYP4F2 CC基因型患者〔（3.37±0.68） mg vs.（2.94±0.74） mg，P<0.05〕；同基因型患者，INR未达标组CYP4F2 CC〔（4.02±0.58） mg vs.（2.94±0.74） mg〕和CYP4F2 CT基因型〔（4.15±0.88） mg vs.（3.18±0.82） mg〕患者华法林的初始剂量大于INR达标组患者（P<0.05）。纳入性别，年龄，体质量指数（BMI），合并疾病（高血压，糖尿病，冠心病，房颤），细胞色素P-450 2C9（CYP2C9）、CYP4F2和维生素K过氧化物还原酶复合体1（VKORC1）基因多态性以及INR达标与否等因素进行多元线性回归分析，回归方程为：华法林初始剂量（mg）=−8.634+0.352×BMI（kg/m2）+1.102×CYP4F2基因型（CC或CT取值1，TT取值2）+2.147×VKORC1（AA或AG取值1，GG取值2）+1.325×INR（达标取值0，不达标取值1），回归方程的决定系数 R2=0.431（P<0.05）。
      结论  CYP4F2基因多态性对心脏机械瓣膜置换术后患者的华法林初始剂量有影响，同时该作用也受机体特征和其他因素的影响。

     

    Abstract:
      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.

     

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