Influence of APOE Gene Polymorphism on Interindividual and Interethnic Warfarin Dosage Requirement: A Systematic
Wan-Ying Yu1, Xue Sun2, Mia Wadelius3
1Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Background:
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.
Methods:
Revman 5.3 software was used to analyze the relationship between APOE genotypes and warfarin dose requirements.
Results:
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.
Conclusion:
This is the first meta-analysis of the association between APOE genotypes and warfarin dose. APOE E2/E2 might be one of the factors affecting warfarin dose requirements. The effect of APOE may vary between ethnicities.
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