Influence of CYP2C9 and VKORC1 1173C/T genotype on the risk of hemorrhagic complications in African-American and European-American patients on warfarin

被引：187

作者：

Limdi, Na ^{[1
]}

McGwin, G. ^{[2
]}

Goldstein, J. A. ^{[3
]}

Beasley, T. M. ^{[4
,5
]}

Arnett, D. K. ^{[2
]}

Adler, B. K. ^{[6
]}

Baird, M. F. ^{[7
]}

Acton, R. T. ^{[8
,9
,10
,11
]}

机构：

[1] Univ Alabama, Dept Neurol, Birmingham, AL 35294 USA

[2] Univ Alabama, Dept Epidemiol, Birmingham, AL USA

[3] Univ Alabama, Natl Inst Environm Hlth Sci, Lab Pharmacol & Chem, Birmingham, AL USA

[4] Univ Alabama, Dept Biostat, Sect Stat Genet, Birmingham, AL 35294 USA

[5] Univ Alabama, Dept Biostat, Sect Stat Genet, Birmingham, AL 35294 USA

[6] Univ Alabama, So Hematol & Oncol PC, Birmingham, AL USA

[7] Univ Alabama, Dept Hematol & Oncol, Birmingham, AL USA

[8] Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA

[9] Univ Alabama, Dept Med, Birmingham, AL 35294 USA

[10] Univ Alabama, Dept Genet, Birmingham, AL USA

[11] Univ Alabama, Dept Epidemiol & Int Hlth, Birmingham, AL USA

来源：

CLINICAL PHARMACOLOGY & THERAPEUTICS | 2008年 / 83卷 / 02期

关键词：

D O I：

10.1038/sj.clpt.6100290

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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.

引用

页码：312 / 321

页数：10

共 52 条

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