The influence of genetic polymorphisms and interacting drugs on initial response to warfarin in Chinese patients with heart valve replacement
The influence of genetic polymorphisms and interacting drugs on initial response to warfarin in Chinese patients with heart valve replacement
复制标题
基因多态性和相互作用药物对中国心脏瓣膜置换术患者华法林初始反应的影响
DOI：
10.1007/s00228-011-0995-6
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发表时间：
2011-02
影响因子：
2.9
通讯作者：
Lin, Shu-Guang
中科院分区：
文献类型：
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作者：
Zhong, Shi-Long;Liu, Yuan;Yu, Xi-Yong;Xu, Dan;Tan, Hong-Hong;Lin, Qiu-Xiong;Yang, Min;Lao, Hai-Yan;Lin, Shu-Guang
与遗传因素相比，华法林的药物相互作用在药物遗传学研究中还很少见。本研究旨在系统研究VKORC 1、STX4A、CYP2C9、CYP3A4和GGCX基因多态性及相互作用药物对中国心脏瓣膜置换术（HVR）患者华法林初始疗效的影响。12种多态性和47种药物与首次国际标准化比值（INR）≥ 1.8和> 3.5的时间的主要结局以及时间INR <1.8的比例、时间INR> 3.5的比例的次要结局的关系，结果基因多态性和相互作用药物可显著影响主要和次要结局。体表面积（BSA）、VKORC1g.3588G> A等位基因和CYP2C9 * 3等位基因显著影响至首次INR ≥ 1.8的时间，风险比（HR; 95%可信区间[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INR> 3.5的时间不仅受BSA、VKORC1g.3588G> A等位基因和CYP2C9 * 3等位基因的影响，HR（95%CI）为0.26（0.07 - 0.99）、2.76（1.61 - 4.72）和3.09（2.02 - 4.74），但也与年龄和相互作用的药物，包括氟康唑，胺碘酮，和辛伐他汀，HR（95%CI）为1.02（1.01 - 1.04）、2.66（1.16 - 6.08）、1.78（1.17 - 2.73）和5.33结论不仅VKORC 1和CYP2C9基因型，而且相互作用药物，对华法林初始反应的变异性有显著影响。
PurposeCompared with genetic factors, drug interactions were largely unexplored in warfarin pharmacogenetic studies. This study sought to systematically investigate the effects of genetic polymorphisms ofVKORC1,STX4A,CYP2C9,CYP3A4, andGGCXand interacting drugs on the initial responses to warfarin in Chinese patients with heart valve replacement (HVR).MethodsA 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.ResultsGenetic 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),VKORC1g.3588G > A allele, andCYP2C9*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,VKORC1g.3588G > A allele, andCYP2C9*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.ConclusionsNot onlyVKORC1andCYP2C9genotypes, but also interacting drugs, had a significant impact on the variability of the initial response to warfarin.
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DOI：
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发表时间：
1996-04
期刊：
Drug metabolism and disposition: the biological fate of chemicals
影响因子：
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作者：
D. Black;K. Kunze;L. Wienkers;B. Gidal;T. Seaton;N. Mcdonnell;J. Evans;J. Bauwens;William F. Trager
通讯作者：
D. Black;K. Kunze;L. Wienkers;B. Gidal;T. Seaton;N. Mcdonnell;J. Evans;J. Bauwens;William F. Trager
影响因子：
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作者：
N. Kerin;R. Blevins;L. Goldman;K. Faitel;M. Rubenfire
通讯作者：
N. Kerin;R. Blevins;L. Goldman;K. Faitel;M. Rubenfire
DOI：
10.1007/s10928-009-9138-4
发表时间：
2010-02-01
影响因子：
2.5
作者：
Yuen, Eunice;Gueorguieva, Ivelina;Aarons, Leon
通讯作者：
Aarons, Leon
影响因子：
2.6
作者：
Surachai Kotirum;N. Chaiyakunapruk;Katechan Jampachaisri;Supharat Wattanasombat;P. Rojnuckarin
通讯作者：
Surachai Kotirum;N. Chaiyakunapruk;Katechan Jampachaisri;Supharat Wattanasombat;P. Rojnuckarin
影响因子：
6.7
作者：
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