title: Influence of APOE Gene Polymorphism on Interindividual and Interethnic Warfarin Dosage Requirement: A Systematic Review and Meta-Analysis.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Wan-Ying
authors.initials: WY
authors.lastname: Yu
authors.affiliation: Center of Clinical Pharmacology, the Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Medical Sciences, Clinical Pharmacology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Mia
authors.initials: M
authors.lastname: Wadelius
authors.affiliation: Center for Medical Experiments, Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Huang
authors.affiliation: Institute of Pharmacy & Pharmacology, University of South China, Hengyang, Hunan, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Peng
authors.affiliation: Center of Clinical Pharmacology, the Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Wan-le
authors.initials: WL
authors.lastname: Ma
authors.affiliation: Center of Clinical Pharmacology, the Third Xiangya Hospital, Central South University, Changsha, Hunan, China. ygp9880@126.com.
authors.forename: Guo-Ping
authors.initials: GP
authors.lastname: Yang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage* / Q000378:metabolism; D001057:Apolipoproteins E / Q000235:genetics*; D001777:Blood Coagulation / Q000187:drug effects* / Q000235:genetics; D016009:Chi-Square Distribution; D054796:Drug Dosage Calculations; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D000071184:Pharmacogenomic Variants; D010641:Phenotype; D011110:Polymorphism, Genetic; D014859:Warfarin / Q000008:administration & dosage* / Q000378:metabolism
chemical_list: D000925:Anticoagulants; D001057:Apolipoproteins E; D014859:Warfarin
keywords: APOE; Dose requirement; Gene polymorphism; Meta-analysis; Systematic review; Warfarin