Li Jiao, Yang Wenlong, Xie Zhonghui, Yu Kun, Chen Yuhua, Cui Kaijun
College of Life Science, Sichuan Normal University, Chengdu, People's Republic of China.
Department of Cardiology, West China Hospital, Sichuan University, Chengdu, People's Republic of China.
BMC Cardiovasc Disord. 2018 May 18;18(1):96. doi: 10.1186/s12872-018-0837-x.
The anticoagulation of atrial fibrillation catheter ablation during the perioperative stage does matter and should be treated with discretion. We aimed to assess impact of three important genes participating in vitamin K cycle (i.e. VKORC1 rs9923231, CYP4F2 rs2108622 and NQO1 rs1800566) on the daily stable warfarin dose requirement in Sichuan Han Chinese patients with catheter ablation of atrial fibrillation.
A total of 222 atrial fibrillation patients taking stable warfarin therapy after catheter ablation operation were enrolled in this study. The study population included had high (≥2) risk according to the CHA2DS2-VASc risk score. Genotypes of VKORC1 rs9923231, CYP4F2 rs2108622 and NQO1 rs1800566 were analyzed by using the polymerase chain reaction restriction fragment length polymorphism method (PCR-RFLP). Multiple linear regression analysis was applied to depict the impact of VKORC1 rs9923231, CYP4F2 rs2108622 and NQO1 rs1800566 on the daily stable warfarin dose requirement.
Carriers of VKORC1 rs9923231 AG/GG genotypes required significantly higher warfarin dose (3.03 ± 0.28 mg/day, 7.19 mg/day, respectively) than AA carriers (2.52 ± 0.07 mg/day; P < 0.001). Carriers of CYP4F2 rs2108622 CT/TT genotypes required significantly higher warfarin dose (3.38 ± 0.22 mg/day, 2.79 ± 0.19 mg/day, respectively) than CC carriers (2.41 ± 0.08 mg/day; P < 0.001). However, the warfarin dose for carriers of NQO1 rs1800566 CT/TT genotypes (2.46 ± 0.24 mg/day, 3.01 ± 0.27 mg/day, respectively) was not significantly higher than that for the CC carriers (2.33 ± 0.1 mg/day). The multiple linear regression model including genotypes and demographic characteristics, could explain 20.1% of individual variations in the daily stable warfarin dose in Sichuan Han Chinese. VKORC1 rs9923231 contributed most (15%) to the individual variations in daily stable warfarin dose, while CYP4F2 rs2108622 contributed least (3%).
NQO1 rs1800566 is not a significant genetic factor of warfarin dose for Han Chinese, whereas VKORC1 rs9923231 and CYP4F2 rs2108622 are significant genetic factors, which could explain 15% and approximately 3% of individual variations in the daily stable warfarin dose respectively.
心房颤动导管消融围手术期的抗凝治疗至关重要，应谨慎处理。我们旨在评估参与维生素K循环的三个重要基因（即VKORC1 rs9923231、CYP4F2 rs2108622和NQO1 rs1800566）对四川汉族心房颤动导管消融患者每日稳定华法林剂量需求的影响。
本研究共纳入222例导管消融术后接受稳定华法林治疗的心房颤动患者。根据CHA2DS2-VASc风险评分，研究人群具有高（≥2）风险。采用聚合酶链反应-限制性片段长度多态性方法（PCR-RFLP）分析VKORC1 rs9923231、CYP4F2 rs2108622和NQO1 rs1800566的基因型。应用多元线性回归分析描述VKORC1 rs9923231、CYP4F2 rs2108622和NQO1 rs1800566对每日稳定华法林剂量需求的影响。
VKORC1 rs9923231 AG/GG基因型携带者所需华法林剂量（分别为3.03±0.28mg/天、7.19mg/天）显著高于AA携带者（2.52±0.07mg/天；P<0.001）。CYP4F2 rs2108622 CT/TT基因型携带者所需华法林剂量（分别为3.38±0.22mg/天、2.79±0.19mg/天）显著高于CC携带者（2.41±0.08mg/天；P<0.001）。然而，NQO1 rs1800566 CT/TT基因型携带者的华法林剂量（分别为2.46±0.24mg/天、3.01±0.27mg/天）并不显著高于CC携带者（2.33±0.1mg/天）。包含基因型和人口统计学特征的多元线性回归模型可以解释四川汉族每日稳定华法林剂量个体差异的20.1%。VKORC1 rs9923231对每日稳定华法林剂量个体差异的贡献最大（15%），而CYP4F2 rs2108622的贡献最小（3%）。
对于汉族人群，NQO1 rs1800566不是华法林剂量的显著遗传因素，而VKORC1 rs9923231和CYP4F2 rs2108622是显著遗传因素，它们分别可以解释每日稳定华法林剂量个体差异的15%和约3%。
