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

Cardiovasc Ther. 2016 Oct;34(5):297-307. doi: 10.1111/1755-5922.12186.

Abstract

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.

Keywords: APOE; Dose requirement; Gene polymorphism; Meta-analysis; Systematic review; Warfarin.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anticoagulants / administration & dosage*
  • Anticoagulants / metabolism
  • Apolipoproteins E / genetics*
  • Blood Coagulation / drug effects*
  • Blood Coagulation / genetics
  • Chi-Square Distribution
  • Drug Dosage Calculations
  • Ethnicity / genetics*
  • Female
  • Gene Frequency
  • Genotype
  • Humans
  • International Normalized Ratio
  • Male
  • Middle Aged
  • Pharmacogenetics
  • Pharmacogenomic Variants
  • Phenotype
  • Polymorphism, Genetic*
  • Warfarin / administration & dosage*
  • Warfarin / metabolism

Substances

  • Anticoagulants
  • Apolipoproteins E
  • Warfarin