Impact of VKORC1, CYP4F2 and NQO1 gene variants on warfarin dose requirement in Han Chinese patients with catheter ablation for atrial fibrillation.
Impact of VKORC1, CYP4F2 and NQO1 gene variants on warfarin dose requirement in Han Chinese patients with catheter ablation for atrial fibrillation.
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DOI：
10.1186/s12872-018-0837-x
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发表时间：
2018-05-18
影响因子：
2.1
通讯作者：
Cui K
中科院分区：
文献类型：
--
作者：
Li J;Yang W;Xie Z;Yu K;Chen Y;Cui K
房颤导管消融术围手术期的抗凝治疗确实重要，应谨慎处理。我们的目的是评估参与维生素K循环的三个重要基因（即VKORC 1 rs 9923231、CYP 4F 2 rs 2108622和NQO 1 rs 1800566）对中国四川汉族房颤导管消融患者每日稳定华法林剂量需求的影响。222例房颤患者在导管消融术后服用稳定的华法林治疗。根据CHA 2DS 2-VASc风险评分，纳入的研究人群具有高（≥2）风险。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法分析VKORC 1 rs 9923231、CYP 4F 2 rs 2108622和NQO 1 rs 1800566基因型。采用多元线性回归分析描述VKORC 1 rs 9923231、CYP 4F 2 rs 2108622和NQO 1 rs 1800566对每日稳定华法林剂量需求的影响。VKORC 1 rs 9923231 AG/GG基因型携带者需要的华法林剂量（分别为3.03 ± 0.28 mg/d、7.19 mg/d）显著高于AA携带者（2.52 ± 0.07 mg/d; P < 0.001）。CYP 4F 2 rs 2108622 CT/TT基因型携带者需要的华法林剂量（分别为3.38 ± 0.22 mg/d、2.79 ± 0.19 mg/d）显著高于CC基因型携带者（2.41 ± 0.08 mg/d; P < 0.001）。然而，NQO 1 rs 1800566 CT/TT基因型携带者的华法林剂量（分别为2.46 ± 0.24 mg/d，3.01 ± 0.27 mg/d）并不显著高于CC携带者（2.33 ± 0.1 mg/d）。包括基因型和人口统计学特征的多元线性回归模型可以解释20.1%的四川汉族华法林日稳定剂量个体差异。VKORC 1 rs 9923231对华法林每日稳定剂量的个体差异贡献最大（15%），而CYP 4F 2 rs 2108622贡献最小（3%）。NQO 1 rs 1800566不是中国汉族人华法林剂量的显著遗传因素，而VKORC 1 rs 9923231和CYP 4F 2 rs 2108622是显著遗传因素，分别可以解释15%和约3%的华法林每日稳定剂量的个体变异。
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.
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影响因子：
3.4
作者：
Cen, Han-Jing;Zeng, Wu-Tao;Zhao, Li-Zi
通讯作者：
Zhao, Li-Zi
DOI：
10.1111/j.1742-7843.2006.pto_440.x
发表时间：
2006-06-01
影响因子：
3.1
作者：
Larramendy-Gozalo, Claire;Yang, Jue Quin;Becquemont, Laurent
通讯作者：
Becquemont, Laurent
影响因子：
20.3
作者：
Sconce, EA;Khan, TI;Kamali, F
通讯作者：
Kamali, F
影响因子：
2.1
作者：
Singh, Onkar;Sandanaraj, Edwin;Chowbay, Balram
通讯作者：
Chowbay, Balram
CYP2C9 和 VKORC1 对患者对华法林反应的影响：系统评价和荟萃分析。
影响因子：
3.7
作者：
Jorgensen AL;FitzGerald RJ;Oyee J;Pirmohamed M;Williamson PR
通讯作者：
Williamson PR