Association between apolipoprotein E genotype and warfarin response during initial anticoagulation

Apolipoprotein E (APOE) genotypes are associated with warfarin dose requirements in various populations. Whether APOE genotypes mediate the warfarin response is unknown. The aim of this study was to evaluate the genetic contributions of different APOE genotypes to the early phase of anticoagulation in Han Chinese patients. We conducted a retrospective cohort study and assessed APOE genotypes, clinical characteristics, international normalized ratio (INR) responses, warfarin dose requirements and bleeding events in 429 Han Chinese patients. The study outcomes were the time to the first INR within the therapeutic range, the time to the first INR of more than 4, the INR response over time, and the warfarin dose requirement. Compared with patients with the epsilon 3/epsilon 3 genotype, patients with at least one epsilon 4 allele had significantly longer times to the first INR of more than 4 during both the initial 20 days (P = 0.001, HR 2.9; 95% CI, 1.54-5.45) and the entire follow-up period (P < 0.001, HR 3.26; 95% CI, 1.94-5.47), but this allele was not a significant predictor of the time to the first INR within the therapeutic range. No association was observed between the epsilon 2 allele and INR response, and both the epsilon 4 allele and the epsilon 2 allele did not significantly affect the required warfarin dose during the follow-up. These observations suggest that genetic variants of APOE are associated with an increased risk of overanticoagulation among the Han Chinese population. However, these variants may not be useful in predicting warfarin maintenance dose requirements.