1. ¹Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics & Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
2. ²Department of Pharmacology and Center for Pharmacogenetics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
3. ³Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
4. ⁴Department of Medicine and Veterans Affairs Medical Center, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA

Correspondence: SE Kimmel, (skimmel@cceb.med.upenn.edu)

Received 14 November 2006; Accepted 17 January 2007; Published online 28 February 2007.

Abstract

The objective of this study was to determine whether two vitamin K epoxide reductase complex 1 (VKORC1) polymorphisms contribute to the variability in warfarin response, particularly in African Americans. The effect of the VKORC1 1173C/T and -1639G/A polymorphisms was examined in a prospective cohort study of 338 warfarin users. Subjects carrying an 1173T allele had a lower warfarin maintenance dose compared with subjects with the CC genotype in African Americans (-12.10 mg/week4.93; P=0.02) and Caucasians (-14.41 mg/week3.28; P<0.001). Before reaching maintenance dose, only Caucasians with the T allele had significantly increased risk of international normalized ratio >3 (odds ratio=3.10; 95% confidence interval: 1.73–5.55) compared with Caucasians with the CC genotype. Polymorphisms in the VKORC1 gene are associated with warfarin maintenance dose requirements among both African Americans and Caucasians. However, these polymorphisms may not be as useful in predicting over-anticoagulation among African Americans.