Influence of APOE Gene Polymorphism on Interindividual and Interethnic Warfarin Dosage Requirement: A Systematic Review and Meta-Analysis.

Abstract

Warfarin is the most extensively used coumarin anticoagulant. It has been shown that the anticoagulant effect of warfarin is associated with genetic variation. Apolipoprotein E (ApoE) is a possible candidate to influence the maintenance dose of warfarin. ApoE affects the vitamin K cycle by mediating the uptake of vitamin K into the liver. The vitamin K cycle is the drug target of warfarin. However, the association between genetic variants of the APOE gene and warfarin dose requirement is still controversial. Revman 5.3 software was used to analyze the relationship between APOE genotypes and warfarin dose requirements. In our meta-analysis, the E2/E2 genotype was significantly associated with warfarin dose. E2/E2 patients required 12% (P=0.0002) lower mean daily warfarin dose than E3/E3 carriers. In addition, subgroup analysis showed that Asians with the E4/E4 genotype tended to need lower warfarin maintenance doses, while the African American E4/E4 carriers needed slightly higher doses than E3/E3 carriers; however, these subgroups were very small. This is the first meta-analysis of the association between APOE genotypes and warfarin dose. APOE E2/E2 might be one of thefactors affecting warfarin dose requirements. The effect of APOE may vary between ethnicities.