1. ¹Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama, USA
2. ²Department of Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama, USA
3. ³Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, University of Alabama at Birmingham, Birmingham, Alabama, USA
4. ⁴Section on Statistical Genetics, Department of Biostatistics, University of Alabama at Birmingham, Birmingham, Alabama, USA
5. ⁵Southern Hematology and Oncology, PC, University of Alabama at Birmingham, Birmingham, Alabama, USA
6. ⁶Department of Hematology and Oncology, University of Alabama at Birmingham, Birmingham, Alabama, USA
7. ⁷Departments of Microbiology, Medicine, Genetics, Epidemiology and International Health, University of Alabama at Birmingham, Birmingham, Alabama, USA

Correspondence: NA Limdi, (nlimdi@uab.edu)

Received 23 February 2007; Accepted 7 June 2007; Published online 25 July 2007.

Abstract

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 (60.615.6 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.