title: APOE genotype makes a small contribution to warfarin dose requirements.
abstract: Alterations in vitamin K availability can significantly influence anticoagulation response to warfarin. Apolipoprotein E (APOE) plays a part in the hepatic uptake of lipid-soluble vitamin K. This study aimed to determine the influence of common polymorphisms in the APOE gene on warfarin dose requirements. patients with stable anticoagulation control and with a target International Normalized Ratio (INR) 2.0-3.0 were genotyped for the APOE epsilon2, epsilon3 and epsilon4 variants. Mean +/- SD daily warfarin doses were significantly lower in patients carrying at least one epsilon4 allele compared to the epsilon3epsilon3 reference genotype (3.3 +/- 1.9 versus 4.0 +/- 1.8; P = 0.03; 95% CI: 0.1-1.2). Multivariate regression analysis showed that patient age, height and CYP2C9, VKORC1 and APOE genotypes significantly contributed to warfarin dose requirement (R = 57%). only the epsilon4 allele of APOE was found to make a significant (P = 0.002) but small contribution to warfarin dose requirement. There was no significant difference in fasted plasma vitamin K concentration between patients with the different APOE genotypes. This study suggests that APOE genotype is unlikely to have a clinically significant effect on warfarin dose requirements.
authors.affiliation: School of Clinical and Laboratory Sciences, University of Newcastle upon Tyne, Newcastle upon Tyne, UK.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Sconce
authors.forename: Ann K
authors.initials: AK
authors.lastname: Daly
authors.forename: Tayyaba I
authors.initials: TI
authors.lastname: Khan
authors.forename: Hilary A
authors.initials: HA
authors.lastname: Wynne
authors.forename: Farhad
authors.initials: F
authors.lastname: Kamali
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000627:therapeutic use; D001057:Apolipoproteins E / Q000235:genetics* / Q000502:physiology; D001778:Blood Coagulation Disorders / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000502:physiology; D014813:Vitamin K Deficiency / Q000188:drug therapy* / Q000235:genetics; D014859:Warfarin / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D001057:Apolipoproteins E; D014859:Warfarin