Influence of CYP2C9 and VKORC1 1173C/T genotype on the risk of hemorrhagic complications in African-American and European-American patients on warfarin
Influence of CYP2C9 and VKORC1 1173C/T genotype on the risk of hemorrhagic complications in African-American and European-American patients on warfarin
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DOI：
10.1038/sj.clpt.6100290
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发表时间：
2008-02-01
影响因子：
6.7
通讯作者：
Acton, R. T.
中科院分区：
文献类型：
--
作者：
Limdi, Na;McGwin, G.;Acton, R. T.
本研究报告了非裔美国人和欧洲裔美国人中CYP2C9和VKORC1173C/T基因与出血风险的关系。使用COX比例风险回归对人口统计学、共病和随时间变化的协变量进行调整，对这种相关性进行评估。在446名患者(60.6岁+/-15.6岁，50%男性，227名非裔美国人)中，44名大出血和203名轻微出血发生在555人年中。变异的CYP2C9基因增加了大出血(危险比(HR)3.0；95%可信区间(CI)：1.1-8.0)的风险，但不会增加轻微(HR 1.3；95%CI：0.8-2.1)出血的风险。治疗稳定前大出血风险增加5.3倍(95%CI：0.4~64.0)，稳定后增加2.2倍(95%CI：0.7~6.5)，抗凝不稳定时增加2.4倍(95%CI：0.8~7.4)。变异的VKORC1173C/T基因没有显著增加大出血(HR 1.7；95%CI：0.7-4.4)或轻微出血(HR 0.8；95%CI：0.5-1.3)的风险。CYP2C9基因变异与大出血风险增加有关，即使在治疗稳定后这种情况也会持续存在。
The association of CYP2C9 and VKORC1 1173C/T genotype and risk of hemorrhage among African Americans and European Americans is presented. This association was evaluated using Cox proportional hazard regression with adjustment for demographics, comorbidity, and time-varying covariates. Forty-four major and 203 minor hemorrhages occurred over 555 person-years among 446 patients (60.6 +/- 15.6 years, 50% men, 227 African Americans). The variant CYP2C9 genotype conferred an increased risk for major (hazard ratio (HR) 3.0; 95% confidence interval (CI): 1.1-8.0) but not minor (HR 1.3; 95% CI: 0.8-2.1) hemorrhage. The risk of major hemorrhage was 5.3-fold (95% CI: 0.4-64.0) higher before stabilization of therapy, 2.2-fold (95% CI: 0.7-6.5) after stabilization, and 2.4-fold (95% CI: 0.8-7.4) during all periods when anticoagulation was not stable. The variant VKORC1 1173C/T genotype did not confer a significant increase in risk for major (HR 1.7; 95% CI: 0.7-4.4) or minor (HR 0.8; 95% CI: 0.5-1.3) hemorrhage. The variant CYP2C9 genotype is associated with an increased risk of major hemorrhage, which persists even after stabilization of therapy.