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Influence of CYP2C9 and VKORC1 1173C/T Genotype on the Risk of Hemorrhagic Complications in African‐American and European‐American Patients on Warfarin
Author(s) -
Limdi NA,
McGwin G,
Goldstein JA,
Beasley TM,
Arnett DK,
Adler BK,
Baird MF,
Acton RT
Publication year - 2008
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/sj.clpt.6100290
Subject(s) - medicine , hazard ratio , genotype , confidence interval , warfarin , proportional hazards model , cyp2c9 , lower risk , gastroenterology , vkorc1 , atrial fibrillation , biology , cytochrome p450 , metabolism , gene , biochemistry
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. Clinical Pharmacology & Therapeutics (2008) doi: 10.1038/sj.clpt.6100290