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首页> 外文期刊>European journal of clinical pharmacology >The influence of genetic polymorphisms and interacting drugs on initial response to warfarin in Chinese patients with heart valve replacement.
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The influence of genetic polymorphisms and interacting drugs on initial response to warfarin in Chinese patients with heart valve replacement.

机译：遗传多态性和相互作用药物对中国心脏瓣膜置换患者华法林初始反应的影响。

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PURPOSE: Compared with genetic factors, drug interactions were largely unexplored in warfarin pharmacogenetic studies. This study sought to systematically investigate the effects of genetic polymorphisms of VKORC1, STX4A, CYP2C9, CYP3A4, and GGCX and interacting drugs on the initial responses to warfarin in Chinese patients with heart valve replacement (HVR). METHODS: A retrospective study was conducted in 809 patients starting warfarin therapy after HVR. The relationships between 12 polymorphisms plus 47 drugs and primary outcomes of the time to the first international normalized ratio (INR) >/= 1.8 and the time to the first INR > 3.5 and the secondary outcomes of the proportion of time INR < 1.8, the proportion of time INR > 3.5, and the daily warfarin dose in the first 28 days after the initiation of warfarin treatment were analyzed. RESULTS: Genetic polymorphisms and interacting drugs could significantly affect the primary and secondary outcomes. The time to the first INR >/= 1.8 was significantly influenced by the body surface area (BSA), VKORC1 g.3588G > A allele, and CYP2C9*3 allele, with hazard ratio (HR; 95% confidence interval [CI]) of 0.34 (0.17-0.66), 2.71 (2.2-3.35) and 1.43 (1.07-1.93) respectively. The time to the first INR > 3.5 was affected not only by BSA, VKORC1 g.3588G > A allele, and CYP2C9*3 allele with HR (95%CI) of 0.26 (0.07-0.99), 2.76 (1.61-4.72), and 3.09 (2.02-4.74) respectively, but also by age and interacting drugs, including fluconazole, amiodarone, and simvastatin with HR (95%CI) of 1.02 (1.01-1.04), 2.66 (1.16-6.08), 1.78 (1.17-2.73), and 5.33 (1.67-16.96) respectively. CONCLUSIONS: Not only VKORC1 and CYP2C9 genotypes, but also interacting drugs, had a significant impact on the variability of the initial response to warfarin.
机译：目的：与遗传因素相比，在华法林的药物遗传学研究中药物相互作用在很大程度上尚未被探索。这项研究试图系统研究VKORC1，STX4A，CYP2C9，CYP3A4和GGCX和相互作用药物的遗传多态性对中国有心脏瓣膜置换术（HVR）患者对华法林初始反应的影响。方法：对809例HVR后开始使用华法林治疗的患者进行了回顾性研究。 12种多态性加47种药物与首次国际标准化时间（INR）> / = 1.8的时间和首次INR> 3.5的时间以及INR <1.8的时间的次要结果之间的关系分析了INR> 3.5的时间比例，以及开始使用华法林后28天内的每日华法林剂量。结果：遗传多态性和相互作用的药物可能会显着影响主要和次要结果。首次INR> / = 1.8的时间受身体表面积（BSA），VKORC1 g.3588G> A等位基因和CYP2C9 * 3等位基因的显着影响，危险比（HR; 95％置信区间[CI]）分别为0.34（0.17-0.66），2.71（2.2-3.35）和1.43（1.07-1.93）。首次达到INR> 3.5的时间不仅受到BSA，VKORC1 g.3588G> A等位基因和HR（95％CI）为0.26（0.07-0.99），2.76（1.61-4.72）的CYP2C9 * 3等位基因的影响，和3.09（2.02-4.74），以及年龄和相互作用药物，包括氟康唑，胺碘酮和辛伐他汀，其HR（95％CI）分别为1.02（1.01-1.04），2.66（1.16-6.08），1.78（1.17- 2.73）和5.33（1.67-16.96）。结论：不仅VKORC1和CYP2C9基因型，而且相互作用的药物，对华法林初始反应的变异性都有显着影响。

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